AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2766-2314/155
*Corresponding Author: Elizaveta I Bon, Candidate of biological science, Assistant professor of pathophysiology department named D. A. Maslakov, Grodno State Medical University; Grodno State Medical University, 80 Gorky St,230009, Grodno, Belarus.
Citation: Bon E. I, Maksimovich N.Ye, Zimatkin S.M, Kiskevich P.V, (2025), Integrative Mechanisms of The Cerebellum, J, Biotechnology and Bioprocessing, 6(2); DOI:10.31579/2766-2314/155
Copyright: © 2025, Elizaveta I Bon. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 14 March 2025 | Accepted: 28 March 2025 | Published: 07 April 2025
Keywords: integrative mechanisms; cerebellum; neural structure; synaptic organization
The study of integrative mechanisms of cerebellar activity is currently of great interest. There are undoubtedly a number of reasons for this. These include, first of all, the idea that the cerebellum works like a calculating machine which is based on the following facts. On the other hand, on the basis of studies on animals with the cerebellum removed and observation of people with traumatic its damage, it is known that the cerebellum performs a number of motor functions: a) maintenance of posture and balance; b) maintenance of muscle tone and its redistribution; c) coordination of voluntary movements
The study of integrative mechanisms of cerebellar activity is currently of great interest. There are undoubtedly a number of reasons for this. These include, first of all, the idea that the cerebellum works like a calculating machine which is based on the following facts [1-4].
3.The cerebellar cortex, like the cerebral cortex, perceives almost all types of afferent stimuli and, in turn, influences many parts of the CNS. In addition to the well-studied tactile, proprioceptive, and vestibular inputs, the cerebellum presents interoceptive afferents, as well as inputs of other modalities arriving in the cerebellum through the structures of the trunk and reticular formation [12].
4.Finally, the cerebellar output has a strong influence on the sensorimotor area of the cerebral cortex.
On the other hand, on the basis of studies on animals with the cerebellum removed and observation of people with traumatic its damage, it is known that the cerebellum performs a number of motor functions: a) maintenance of posture and balance; b) maintenance of muscle tone and its redistribution; c) coordination of voluntary movements [13-15]. Although these functions are purely motor in themselves, they nevertheless require the participation of specific sensory inputs in their realization. Thus, setting the correct posture is associated with information coming from the spindles about the state of postural tone, making permanent corrections to balance is transmitted by signals from the vestibular apparatus, and adequate coordination of movements requires additional information from the visual, auditory and other analyzers. In this sense, the cerebellum must be considered as an organ of sensorimotor integration.
Afferent Systems of The Cerebellum
Given the complexity of the integrative mechanisms of the cerebellum, it is appropriate to dwell on a brief description of some features of its structure and synaptic organization.
Structure And Synaptic Organization Cerebellar Cortex
The mammalian cerebellar cortex is relatively simple: it has a 3-layer structure and consists of an outer - molecular layer (approximately 300 μm thick), a middle layer of Purkinje cells (70-100 μm thick) and a granular layer, which is 400-500 μm thick at the apex of the lobe, whereas in the depth of the sulcus it is about 100 μm thick. The cortex contains five cell types (granular, basket cells, stellate cells, Golgi cells, Purkinje cells), of which only the granular cells are excitatory and all others are inhibitory [16-18].
The cross section of Fig. 3.1 shows the branching dendrites of Purkinje cells, basket cells, and stellate cells. The key element of the cerebellum, Purkinje cells, represent a typical example of highly differentiated neurons with extensive dendritic branching and various types of synaptic contacts. Their total number is estimated at 1.2 million [17].
There are three types of inhibitory insertion neurons in the molecular layer: basket, short-axon and long-axon stellate cells. The descending part of the basket cell axon ends in the form of a basket on the lower part of the Purkinje cell body. The axons of the stellate cells establish synaptic contact with the Purkinje cell in the ratio of 17: 1. The granular layer contains Golgi cells in addition to granular cells. The number of granular cells in 1 mm3 is 2.8 -106. The axons of the granular cells ascend to the surface, branch T-shaped^ forming parallel fibers and extend from the branching point about 1.5 mm [19-22].
Over 100,000 parallel fibers form excitatory synapses on the dendrites of the Purkinje cell. Parallel fibers also form excitatory synapses with the dendrites of basket cells, stellate cells, and Golgi cells, on which, likewise, the as well as on neighboring Purkinje cells, collaterals of Purkinje cell axons form weak inhibitory synapses. The weak inhibitory action of Purkinje cell axon collaterals on an adjacent Purkinje cell is one of the essential mechanisms in the localization of cerebellar functions [23-25].
Afferent Fiber Systems
All afferent information reaches the cerebellar cortex by two systems of anatomically separate inputs that terminate on Purkinje cells in the form of mossy and climbing fibers, while the Purkinje cell itself is the only output element of the cerebellum. Recently, however, a third type of afferent endings in the cerebellar cortex, whose chemical transmitter is norepinephrine, has been detected by fluorescence. However, these data have not yet been confirmed [20].
The system of climbing fibers of the cerebellum, first described by Ramon Cahal, is a monosynaptic input that makes direct synaptic contact with the soma and dendrites of the Purkinje cell. Synaptic contact with Purkinje cell dendrites is made by means of spines, the number of which is close to 300 in the frog and 170 in the alligator; this number varies little in the higher classes of vertebrates.The multiplicity of synaptic contacts with the Purkinje cell in each climbing fiber is the main prerequisite for the exceptionally strong synaptic excitatory action of the climbing fiber input. The shapes of these synaptic contacts do not differ significantly in animals at different levels of phylogeny. It follows that the input of climbing fibers changes very little as the CNS evolves. Ontogenetically, the synapse between the climbing fiber and the Purkinje cell is initially established at the level of the soma in the form of a “hood,” which gradually moves upward during postnatal development to the region of the Purkinje cell dendrite. The climbing fibers in their apical part are myelinated, the course of their branching almost repeats the pattern of arborization of the Purkinje cell dendritic tree [24-28].
The activity of climbing fibers, being one of the indicators of cerebellar maturity, is registered earlier in mature animals (guinea pigs) than in immature animals, and its functional maturation is slightly ahead of the maturation of afferent input of mossy fibers. Altman believes that the postnatal morphogenesis of Purkinje cells (dendritic branching, growth of spines) largely depends on the inducing action of satellite cells of the cortex (basket cells, stellate cells, and granular cells).
Climbing fibers establish synaptic contact with Purkinje cell dendrites in a 1: 1 ratio, although other data suggest that this contact is not restricted to a single Purkinje cell. The main source of origin of climbing fibers is considered to be the inferior olive. However, there are indications that even after chronic transection of the olivo-cerebellar pathway, activation of Purkinje cells along the input of climbing fibers in a significant percentage of cells persists [27].
Direct electrical stimulation of olive cells exerts a strong excitatory synaptic effect on the Purkinje cell via climbing fibers. A large VPSP appears, at the top of which there are three to five PDs of decreasing amplitude with a frequency of 300-500/s (it is commonly referred to in the literature as a “complex discharge” or “climbing fiber response”)
Under the action of a basket cell discharge, the number of impulses in such a response can be reduced to one, but it is never possible to obtain complete blockade of additional discharges. This suggests that “basket” inhibition acts as a regulator of the degree of inhibitory suppression only within certain limits.
During the registration of focal activity of the cerebellar cortex layers in response to stimulation of the inferior olive, activation of the granular layer is expressed in the predominance of long-latency positive potentials, whereas in the molecular layer, in the region of dendrites, negativity prevails, reflecting the impulse activity of axons of granular cells and the subsequent discharge of Purkinje cells and other cells of the molecular layer. The comparatively long latent period (4-6 ms) of focal potentials during activation of the climbing input in response to stimulation of the cells of the lower olive is associated with a low conduction velocity (5-20 m/s) along climbing fibers. It has been found that discharge evoked through climbing inputs is accompanied by an inhibitory pause (from 100 to 800 ms) in Purkinje cell activity [26-29]. It is believed that inhibition of Purkinje cells after a complex discharge is associated with the action of basket cells, Golgi cells activated by collaterals of climbing fibers. An indication of this is the possibility of repeated activation of Purkinje cells only within 10-20 ms, whereas at longer intervals, the activation of climbing fibers is accompanied by VSPs of reduced amplitude due to the beginning of the inhibitory action of interneurons. Taking into account that the value of focal potential U3 is a measure of granule cell discharge, it can also serve as an indicator of the degree of inhibition of granule cells by Golgi cells. Thus, the input of climbing fibers has an excitatory-inhibitory effect on Purkinje cells, while basket and stellate cells have only an inhibitory effect on them.
Afferent mossy fibers are found in the cerebellum of all vertebrates. The ends of the mossy fibers form a synaptic contact with the dendrites of granule cells. This type of synapse is called glomerular because the terminal portion of the afferent mossy fiber forms approximately 10 rosettes, allowing contact with an order of magnitude greater number of granule cell dendrites [18]. The exiting axon of the granule cell, T-branching, forms parallel fibers that establish synaptic contact with Purkinje cell dendrites. The system of mossy fibers-grain cells-parallel fibers-Purkinje cell dendrites is basically similar in all vertebrates, but it undergoes significant quantitative growth in phylogeny. This is the reason for the strong development of the molecular layer in higher vertebrates, the sharp increase in the number of synaptic contacts of parallel fibers with Purkinje cells, and the development of the system of inhibitory interneurons (basket cells, stellate cells, and Golgi cells) in the vertebrate cerebellar cortex [20].
Along with the development of the system of inhibitory neurons, the system of collaterals of climbing fibers and axonal collaterals of Purkinje cells has developed greatly in phylogeny. It is interesting to note that synaptic contact between parallel fibers and Purkinje cells matures earlier than that between mossy fiber input and granular cells. Therefore, the maturation sequence of the ascending afferent pathway in ontogeny does not go in the direction from the periphery to Purkinje cells, but in the opposite direction. The sequence of maturation of synaptic contacts of afferent inputs of climbing and mossy fibers to Purkinje cells of the cerebellum in postnatal ontogenesis is also expressed in the fact that axodendritic contacts with spines of Purkinje cells mature later than deep axosomatic contacts [17-19].
Electrophysiological evidence of this is the fact of earlier appearance of Purkinje cell activity* caused by activation of mossy fibers in guinea pigs, kittens, rabbits, rats.
In order to identify the discharge of mossy fibers, a number of criteria are used, among which the most suitable are: a) the frequency of the background discharge of mossy fibers should be within the range of 5-70 imp/s; b) the response to muscle nerve stimulation should include two to five simple peaks with a frequency of 500-800 Hz (the polarity of the biphasic peak should be 3/4 negative) c) the time of occurrence of the evoked peak should precede the negative _/U2 wave of the focal potential; d) the latency time of the response to stimulation of the forelimb nerve should not exceed 3-5 ms; e) the cell activity should be recorded at a microelectrode displacement of up to 100 µm. Fig. 3.3 shows a schematic of Purkinje cell activation via afferent inputs of climbing and fascicular fibers, from which the temporal characteristics of Purkinje cell activation during intra- (a) and extracellular (b) recordings can be seen [15].
There is evidence that mossy fibers transmit to the cerebellum rapid changes in proprioceptive information from peripheral receptors, on the basis of which the Purkinje cell produces appropriate correction impulses.
Mossy fibers originate in many parts of the CNS and consequently transmit a variety of information to the cerebellum. However, the greatest proportion of afferent signaling enters the cerebellum to the cerebellum via the ventral and dorsal dorsal spinocerebellar tracts, lateral reticular and external cuneiform nuclei, vestibular nuclei, and the reticular formation. Irritation of these extracerebellar structures has a mixed excitatory-inhibitory effect on Purkinje cells. Direct activation of the last link of afferent input to the cerebellum - parallel fibers near Purkinje cells - has a predominantly inhibitory effect on Purkinje cells. However, this effect is extremely sensitive and very dependent on the functional state of the superficial layers of the cerebellar cortex, which usually begins to deteriorate 2-3 h after the onset of cortical work [14-16].
The main indicator of a background-active Purkinje cell is the presence of a pulse irregular discharge caused by activation through mossy fibers and registered at the level of dendrites and cell soma. Its frequency in awake animals (cats, monkeys) varies in rather wide ranges (from 3 to 125 and higher imp/s, and on average from 20 to 70 imp/s) depending on the functional state of the object of study, the type of animal, and the place of Purkinje cell registration in the cerebellum. At the same time, the frequency of Purkinje cell activation through climbing fibers or the frequency of complex discharges in awake cats and monkeys is extremely low and ranges on average from 0.33 to 2.5 imp/s. It has been shown that in intact pigeons the mean discharge frequency of simple Purkinje cell peaks averages 49.3 imp/s, ranging from 12.0 to 118.5 imp/s. The standard deviations of the discharge frequency of simple commissures in intact and decerebrated pigeons are 30.5 and 26.5 imp/s, respectively, while their coefficient of variation is close, 0.62 and 0.64. According to their data, the average frequency of complex peaks in Purkinje cells of intact pigeons is 2.61 imp/s, varying from 1.27 to 4.35 imp/s. The same values in decerebrated pigeons are: average 1.96 imp/s, and fluctuate from 0.58 to 3.51 imp/s [9-13].
Thus, under the influence of decerebration the activity of Purkinje cells in both pigeons and cats is somewhat reduced. At the same time, the appearance of simple peaks under decerebration conditions in response to peripheral stimulation is facilitated, whereas the generation of complex discharges to the same type of afferent influence is hampered. The frequency of the background discharge of Purkinje cells increases with age in both mature and immature births, but mainly due to an increase in the frequency of simple peaks.
Nembutalol anesthesia depresses both the background activity of Purkinje cells and that caused by irritation of superficial parallel fibers and bridge structures, but it has almost no effect on the generation of complex peaks caused by direct irritation of the inferior olive. Thiopental anesthesia has a somewhat weaker effect on the background activity of Purkinje cells [5].
he activity of Purkinje cells in the anterior lobe of the cerebellum changes markedly during sleep. The activity arriving via mossy fibers is particularly enhanced during the paradoxical phase of sleep compared to the phase of synchronized sleep, and it is the stronger the more pronounced the REM phase. The activity of the climbing input of Purkinje cells also changes during paradoxical sleep, but in different ways: in some cells it increases and in others it decreases; however, since the frequency of simple peaks is many times higher than the frequency of complex peaks, the total flux of Purkinje cell activity always increases during paradoxical sleep. The increased activity of Purkinje cells of the inhibitory area of the cerebellum during paradoxical sleep is attributed to the change in tone that occurs during this stage of sleep [8-11].
Reactions Of Purkinje Cells to Afferent Stimuli
For a long time, many physiologists believed that the successful work of the cerebellum as an organ of regulation and coordination of motor activity should be combined with its performance of sensory functions. Numerous physiological experiments of recent years, conducted on representatives of all classes of animals, convince us of this. This is expressed in the reactions of Purkinje cells and cerebellar cortex in response to the arrival of afferent waves of various modalities and in different species of animals: in fish, amphibians, reptiles, birds and mammals [14].
One of the important features of afferent input to the cerebellum is the more pronounced spatial and temporal efficiency of the synaptic action of cutaneous as compared to the action of muscle afferents. These differences are most clearly manifested during suprathreshold stimulation of cutaneous-muscular afferents and registration of total discharge frequency distribution curves. On the entire path of the afferent wave to the Purkinje cell, the greatest difficulties for the passage of the wave are created at the place of synaptic contact of afferent endings of mossy fibers with dendrites of granular cells. The obstacle in this place is best overcome not by single, but by a short series of impulses, which causes discharge of granular cells [20-22].
The study of the nature of convergence of the mossy afferent input to Purkinje cells revealed great diversity in the reactions of the latter to stimulation of the nerves of the limbs. On one Purkinje cell can converge the influences coming through the mossy fibers from the anterior and posterior limbs, and sometimes two Purkinje cells, which are in close proximity, give opposite reactions - one is inhibited and the other is excited under the influence of the same modality of stimulation. It has also been shown that there is overlap and convergence of climbing fibers to the same Purkinje cell activated from different nerves of the fore and hind limbs [26].
If we assume that a stimulus of one modality can activate the inputs of both fascicular and climbing fibers, it seems interesting to investigate the mechanism of the relationship between these two inputs on the same Purkinje cell. It is known that irritation of limb nerves, muscle tendons, or activation of vestibular, visual receptors can change the frequency of discharge of inputs of both mossy and climbing fibers. The highest discharge frequency of complex peaks was recorded in response to caloric stimulation of the labyrinth and was 9 imp/s. This high frequency had a strong inhibitory effect on the frequency of discharge evoked through mossy fibers. It is known, however, that the number of discharges in the' complex peak can be varied by changing the level of polarization of Purkinje cells, in which case it appears that this may influence the degree of inhibitory effect of the complex peak on the discharge evoked through the mossy fibers, which may be as high as 800 ms. The mechanisms of such depression are considered to be: a) inactivation - mechanisms of electrical excitability ; b) “basket” inhibition as a result of activation of basket cells by axon collaterals of climbing fibers and subsequent hyperpolarization of Purkinje cell - mechanism of direct inhibition; c) finally, activation of Golgi cells by axon collaterals of climbing fibers, as a result of which the effect of mossy fiber input on granular cells is inhibited and the excitability of Purkinje cells to afferent stimuli is reduced (the phenomenon of dysfacilitation) [18-21].
At the same time, it is known that in certain areas of the cerebellum, in response to electrical or natural stimulation of a number of afferent inputs of visual, muscle receptors, and cutaneous mechanoreceptors, activation of the same Purkinje cell via both mossy and climbing fibers is observed. This led to the conclusion that the functional organization of the cerebellar cortex is such as to require some correspondence between the inputs of the climbing and mossy fibers when impulses of the same modality converge to the Purkinje cell. However, according to Llinas et al., in response to direct irritation of the vestibular nerve, activation of Purkinje cells of the vestibulo-cerebellum is carried out only through mossy fibers [26]. This gave rise to the viewpoint that the afferent inputs of mossy and climbing fibers represent two independent channels of information. At the same time, it was shown that mossy and climbing fibers, which are not activated from visual and vestibular receptors, can converge on the same Purkinje cell of the vestibulocerebellum. However, it was later found that if natural maze stimulation was used, the same Purkinje cell of the rabbit cerebellum could be activated via both mossy and climbing fibers.
It has been found that there is a connection between Purkinje cell activity and saccadic eye movements, with the discharge of Purkinje cells of the worm part of the cerebellum (VI-VII) preceding the onset of eye movements by 11-24 ms, and the maximum of Purkinje cell activity corresponding to the time of eye movement onset [14].
Somatotopic Organization of The of Mossy and Climbing Fiber Entrances
A complete review of the somatotopic representation in the cerebellum can be found in the extensive monograph by Dau and Moruzzi. At present, the greatest interest is in identifying the somatotopic distribution of mossy and climbing fiber inputs in the cerebellar cortex. Unfortunately, data on this subject (extracellular and total registration) are limited mainly to the anterior lobes of the cerebellum. There are a number of summaries and papers dealing with somatotopic representation in the cerebellum. Mossy fiber terminations in the form of sagittal bands 1 mm wide are grouped in the anterior lobe of the cerebellum and belong to four main tracts: proprioceptive and exteroceptive components of the cuneo-cerebellar and dorsal dorsal spinocerebellar tracts; rostral and ventral spinocerebellar tracts; and two spinocerebellar pathways with a break in the lateral reticular nucleus [23-25].
A number of functional features of synaptic transmission in neurons of spinal cerebellar tracts were considered in the works of Kostyuk and Zadorozhny and Pyatigorsky and Vasilenko. The endings of climbing fibers in the form of sagittal bands are also concentrated in the anterior lobes and include 17 pathways of climbing fibers (dorsal-olive-brain) passing through the inferior olive. The hind limbs project into the rostral part of the anterior lobe of the cerebellum and the anterior limbs into the caudal part, and in the wormlike part, of the three sagittal bands, two represent the hind limbs and one (medial) represents the anterior limbs. In the intermediate part of the anterior lobe, in addition, there is one mixed area in which all limbs are represented. A similar type of distribution in the cerebellum has been shown when the anterior and posterior limb areas of the sensorimotor cortex are irritated. Each narrow sagittal stripe represents a functional center integrating activity that represents motor function, which is different for different zones. It has been shown that each saggittal stripe of the mossy fiber input is strictly connected to the climbing fiber input, and both of these inputs can report to the Purkinje cell changes in the periphery of the motor apparatus [16].
Efferent Systems of The Cerebellum
Of the five types of neurons in the cerebellar cortex, four are inhibitory, including the only efferent neurons, the Purkinje cells. Therefore, at the output of the cerebellar cortex, the mechanism of restraining its activity, the mechanism of inhibition, rather than the mechanism of triggering the next neuron in the reflex chain acts as the active beginning. This peculiarity imposes its imprint on the construction of the efferent system of the cerebellum; its first two links are in coo-
The inhibitory influence of Purkinje cells is opposed to the tonic excitation of cerebellar nuclei neurons [25-27].
Cortical-Nuclear Projections
Anatomically, the entire mammalian cerebellar cortex is subdivided into three symmetrical longitudinal cortical-nuclear zones: the medial (worm) zone projecting to the medial (fastigial) nucleus and the lateral vestibular nucleus; the intermediate (near-worm) zone projecting to the intermediate nucleus; and the lateral zone projecting to the lateral (dentate) nucleus. The topical principle of the projection of the cerebellar cortex to its nuclei was also revealed in the rostro-caudal direction. The efferent zonal organization of the cerebellar cortex has been shown in embryogenesis and confirmed in the form of homologous zones in the lower standing representatives of the phylogenetic series. Recently, overlap between neighboring projection zones has been found and the projection of one zone to two or three cerebellar nuclei has been shown, which is especially pronounced in the lateral cerebellar zone [17-19]. It is concluded that a gradient of overlap rather than strict boundaries between adjacent longitudinal zones is a general property of the organization of cortical-nuclear projections of the cerebellum. The principle of “multilateral” organization has been put forward, according to which there is a large fractionalization of longitudinal zone projections in the cerebellar cortex. This is consistent with the data on the fine topical distribution of Purkinje cell axons in cerebellar nuclei.
Quantitative analysis of morphological data has shown that each of the two or three terminal branching axons of Purkinje cells has 160-200 terminals. Their total number in all cerebellar nuclei reaches 5.7x10” and they form 11600 terminals on each nuclear neuron. Purkinje cell axons account for approximately 60% of the primary terminals terminating on nuclear neurons. It is shown that about 860 Purkinje cells take part in innervation of one nuclear neuron, and axon branches of one Purkinje cell cover 26-39 nuclear neurons [11].
Electrophysiological study of the effects of cerebellar cortex irritation on the impulse activity of nuclear neurons has in principle confirmed the existence of a longitudinal zonal organization of the cerebellum. The fan-shaped character of the organization of cortical-nuclear connections in both rostro-caudal and medio-lateral directions and the absence of a strict boundary between separate longitudinal aeons were shown, which is in agreement with morphological data. Along with this, an extraordinary fractionality and mosaicism of cortical-nuclear influences, the presence of zones of maximum density of projection to an individual nuclear neuron, and convergent-divergent influences of Pur- kinier cells of the cerebellar cortex were found [30].
Recently, anatomical and electrophysiological methods in cats and monkeys have shown a cerebellar nucleo-cortical projection. This projection is represented by collateral branching of axons of efferent neurons of cerebellar nuclei projecting to extramorbid structures. The projection from the nuclei to the cerebellar cortex is organized according to the topographic principle and is similar in this respect to the cortico-nuclear projection. There is reason to believe that the nucleo-cortical projections end in the granular layer of the cerebellar cortex, as do the mossy fibers. Functionally, this projection may represent an intracerebellar feedback system by which cerebellar output can influence integration in the cerebellar cortex not only through its action on neurons in the trunk nuclei containing cells giving rise to cerebellar afferent fibers, but also directly through afferent nuclear neurons. In this respect it should represent an important complement to the inhibitory cortical-nuclear influence exerted by Purkinje cells [25-27].
The medio-lateral principle of cerebellar organization was confirmed and developed in physiological experiments, which showed that the medial zone is associated mainly with the maintenance of body equilibrium, the intermediate zone with locomotion and the lateral zone with arbitrary movements, i.e., each longitudinal zone acts as a coordinator for a particular type of motor act.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
