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The Olfactory Bulb is a component of the Olfactory System, in which it plays an essential role as an interface between the peripheral components and the cerebral cortex responsible for olfactory interpretation and discrimination. It is in this element that the first selective integration of olfactory stimuli occurs through a complex cell interaction that forwards the received olfactory information to higher cortical centers. Considering its position in the organizational hierarchy of the olfactory system, it is now known that changes in the Olfactory Bulb can lead to olfactory abnormalities. Through imaging techniques, it was possible to establish relationships between the occurrence of changes secondary to brain aging and senility, neurodegenerative diseases, head trauma, and infectious diseases with a decrease in the size of the Olfactory Bulb and in olfactory acuity. In companion animals, this relationship has also been identified, with observations of relations between the cranial conformation, the disposition, size, and shape of the Olfactory Bulb, and the occurrence of structural alterations associated with diseases with different etiologies. However, greater difficulty in quantitatively assessing olfactory acuity in animals and a manifestly smaller number of studies dedicated to this topic maintain a lack of concrete and unequivocal results in this field of veterinary sciences. The aim of this work is to revisit the Olfactory Bulb in companion animals in all its dimensions, review its anatomy and histological characteristics, physiological integration in the olfactory system, importance as a potential early indicator of the establishment of specific pathologies, as well as techniques of imaging evaluation for its in vivo clinical exploration.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon ® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Compared to rodents, sheep offer several attractive features as an experimental model for testing different medical and surgical interventions related to pathological gait caused by neurological diseases and injuries. To use sheep for development of novel treatment strategies in the field of neuroscience, it is key to establish the relevant kinematic features of locomotion in this species. To use sheep for development of novel treatment strategies in the field of neuroscience, it is crucial to understand fundamental baseline characteristics of locomotion in this species. Despite their relevance for medical research, little is known about the locomotion in the ovine model, and next to nothing about the three-dimensional (3D) kinematics of the hindlimb. This study is the first to perform and compare two-dimensional (2D) and 3D hindlimb kinematics of the sagittal motion during treadmill walking in the ovine model. Our results show that the most significant differences took place throughout the swing phase of the gait cycle were for the distal joints, ankle and metatarsophalangeal joint, whereas the hip and knee joints were much less affected. The results provide evidence of the inadequacy of a 2D approach to the computation of joint kinematics in clinically normal sheep during treadmill walking when the interest is centered on the hoof's joints. The findings from the present investigation are likely to be useful for an accurate, quantitative and objective assessment of functionally altered gait and its underlying neuronal mechanisms and biomechanical consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diogo, Camassa, Fonseca, Maltez da Costa, Pereira, Filipe, Couto, Raimondo, Armada-da-Silva, Maurício and Varejão.)

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.

Peripheral nerve injury remains a clinical challenge with severe physiological and functional consequences. Despite the existence of multiple possible therapeutic approaches, until now, there is no consensus regarding the advantages of each option or the best methodology in promoting nerve regeneration. Regenerative medicine is a promise to overcome this medical limitation, and in this work, chitosan nerve guide conduits and olfactory mucosa mesenchymal stem/stromal cells were applied in different therapeutic combinations to promote regeneration in sciatic nerves after neurotmesis injury. Over 20 weeks, the intervened animals were subjected to a regular functional assessment (determination of motor performance, nociception, and sciatic indexes), and after this period, they were evaluated kinematically and the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed confirming the beneficial effects of using these therapeutic approaches. The use of chitosan NGCs and cells resulted in better motor performance, better sciatic indexes, and lower gait dysfunction after 20 weeks. The use of only NGGs demonstrated better nociceptive recoveries. The stereological evaluation of the sciatic nerve revealed identical values in the different parameters for all therapeutic groups. In the muscle histomorphometric evaluation, the groups treated with NGCs and cells showed results close to those of the group that received traditional sutures, the one with the best final values. The therapeutic combinations studied show promising outcomes and should be the target of new future works to overcome some irregularities found in the results and establish the combination of nerve guidance conduits and olfactory mucosa mesenchymal stem/stromal cells as viable options in the treatment of peripheral nerves after injury., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Rui D. Alvites et al.)

Stem/stromal cell-based therapies are a branch of regenerative medicine and stand as an attractive option to promote the repair of damaged or dysfunctional tissues and organs. Olfactory mucosa mesenchymal stem/stromal cells have been regarded as a promising tool in regenerative therapies because of their several favorable properties such as multipotency, high proliferation rate, helpful location, and few associated ethical issues. These cells are easily accessible in the nasal cavity of most mammals, including the rat, can be easily applied in autologous treatments, and do not cope with most of the obstacles associated with the use of other stem cells. Despite this, its application in preclinical trials and in both human and animal patients is still limited because of the small number of studies performed so far and to the nonexistence of a standard and unambiguous protocol for collection, isolation, and therapeutic application. In the present work a validation of a protocol for isolation, culture, expansion, freezing, and thawing of olfactory mucosa mesenchymal stem/stromal cells was performed, applied to the rat model, as well as a biological characterization of these cells. To investigate the therapeutic potential of OM-MSCs and their eventual safe application in preclinical trials, the main characteristics of OMSC stemness were addressed., Competing Interests: The author(s) declare(s) that there are no conflicts of interest regarding the publication of this article., (Copyright © 2020 Rui D. Alvites et al.)

The recovery of walking function following spinal cord injury (SCI) is of major importance to patients and clinicians. In experimental SCI studies, a rat model is widely used to assess walking function, following thoracic spinal cord lesion. In an effort to provide a resource which investigators can refer to when seeking the most appropriate functional assay, the authors have compiled and categorized the behavioral assessments used to measure the deficits and recovery of the gait in thoracic SCI rats. These categories include kinematic and kinetic measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. The present review includes the type of outcome data that they produce, the technical difficulty and the time required to potentially train the animals to perform them, and the need for expensive or highly specialized equipment. The use of multiple kinematic and kinetic parameters is recommended to identify subtle deficits and processes involved in the compensatory mechanisms of walking function after experimental thoracic SCI in rats., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Functional recovery following general nerve reconstruction is often associated with poor results. Comparing to rat and mice experimental studies, there are much fewer investigations on nerve regeneration and repair in the sheep, and there are no studies on this subject using gait analysis in the sheep model as an assessment tool. Additionally, this is the first study evaluating obstacle negotiation and the compensatory strategies that take place at each joint in response to the obstacle during locomotion in the sheep model. This study aims to get kinematic data to serve as a template for an objective assessment of the ankle joint motion in future studies of common peroneal nerve (CP) injury and repair in the ovine model. Our results show that a moderately high obstacle set to 10% of the sheep's hindlimb length was associated to several spatial and temporal strategies in order to increase hoof height during obstacle negotiating. Sheep efficiently cleared an obstacle by increasing knee, ankle and metatarsophalangeal flexion during swing, whereas the hip joint is not affected. This study establishes the bounds of normal motion in the neurologically intact hindlimb when approached and cleared an obstacle and provides baseline data for further studies of peripheral nerve research in the ovine model.

The nasal cavity performs several crucial functions in mammals, including rodents, being involved in respiration, behavior, reproduction, and olfaction. Its anatomical structure is complex and divided into several regions, including the olfactory recess where the olfactory mucosa (OM) is located and where the capture and interaction with the environmental odorants occurs. Among the cells of this region are the OM mesenchymal stem cells (MSCs), whose location raises the possibility that these cells could be involved in the peculiar ability of the olfactory nerve to regenerate continuously throughout life, although this relationship has not yet been confirmed. These cells, like all MSCs, present functional characteristics that make them candidates in new therapies associated with regenerative medicine, namely to promote the regeneration of the peripheral nerve after injury. The availability of stem cells to be therapeutically applied essentially depends on their collection in the tissue of origin. In the case of mice and rat's OM-MSCs, knowledge about the anatomy and histology of their nasal cavity is essential in establishing effective collection protocols. The present article describes the morphological characteristics of rodent's OM and establishes an alternative protocol for access to the olfactory recess and collection of the OM. Anat Rec, 301:1678-1689, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)