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Purpose The main aim of this study was to research new treatments following peripheral nerve injury involving melatonin (Mel), acetyl- l -carnitine (ALCAR), and leptin (Lep) using updated unbiased methods at the stereological and electron microscopic levels. Materials and methods Wistar albino rats were randomly divided into nine equal groups; control (Cont), obese control (OG), obese group exposed to sciatic nerve resection (Gap) (OGG), obese group injected intraperitoneally (i.p.) with Mel (OMG), obese group injected with Mel i.p. with gap (OMGG), obese group injected with Lep i.p. (OLG), obese group injected with Lep i.p. with gap (OLGG), obese group injected with ALCAR i.p. (OAG), and obese group injected with ALCAR i.p. with gap (OAGG). Electromyography (EMG) procedures were performed. Following routine histological procedures, stereological analysis was performed for each group. Results In terms of the number of myelinated axons, high significant increase in OGG was observed compared to OG and Cont (p < 0.01). In addition, a highly significant increase in axon surface area and myelin thickness of OGG compared to OG and Cont (p < 0.01) was noted. A significant decrease in myelin thickness/axon diameter ratio of OGG was found in comparison with the other groups. In terms of latency, there was a highly significant decrease in OGG compared to Cont and OG (p < 0.01). Myelinated axon numbers in OAGG, OMGG and OLGG increased highly significantly compared to other groups (p < 0.01). Latency in OMGG, a highly significant increase, was determined in OMG compared to Cont (p < 0.01). In addition, latency values in OGG were highly significantly greater than in OAC and OAGG (p < 0.01). Conclusion In particular, administration of Lep, Mel and ALCAR as neuroprotective agents may make a positive contribution to regeneration and myelination in obese rats. [ABSTRACT FROM AUTHOR]

Abstract: Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction. Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting. Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat. The chitosan tubes displayed low, medium and high degrees of acetylation (DAI: ∼2%, DA: ∼5%, DAIII: ∼20%) and therefore different degradability and microenvironments for the regenerating nerve tissue. Short and long term investigations were performed demonstrating that the chitosan tubes allowed functional and morphological nerve regeneration similar to autologous nerve grafts. Irrespective of the DA growth factor regulation demonstrated to be the same as in controls. Analyses of stereological parameters as well as the immunological tissue response at the implantation site and in the regenerated nerves, revealed that DAI and DAIII chitosan tubes displayed some limitations in the support of axonal regeneration and a high speed of degradation accompanied with low mechanical stability, respectively. The chitosan tubes combine several pre-requisites for a clinical acceptance and DAII chitosan tubes have to be judged as the most supportive for peripheral nerve regeneration. [Copyright &y& Elsevier]

Summary: In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue–vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair. [Copyright &y& Elsevier]

Summary: Peripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined. [Copyright &y& Elsevier]

Posttraumatic nerve repair and prevention of muscle atrophy represent a major challenge of restorative medicine. Considerable interest exists in the potential therapeutic value of laser phototherapy for restoring or temporarily preventing denervated muscle atrophy as well as enhancing regeneration of severely injured peripheral nerves. Low‐power laser irradiation (laser phototherapy) was applied for treatment of rat denervated muscle in order to estimate biochemical transformation on cellular and tissue levels, as well as on rat sciatic nerve model after crush injury, direct or side‐to‐end anastomosis, and neurotube reconstruction. Nerve cells'' growth and axonal sprouting were investigated in embryonic rat brain cultures. The animal outcome allowed clinical double‐blind, placebo‐controlled randomized study that measured the effectiveness of 780‐nm laser phototherapy on patients suffering from incomplete peripheral nerve injuries for 6 months up to several years. In denervated muscles, animal study suggests that the function of denervated muscles can be partially preserved by temporary prevention of denervation‐induced biochemical changes. The function of denervated muscles can be restored, not completely but to a very substantial degree, by laser treatment initiated at the earliest possible stage post injury. In peripheral nerve injury, laser phototherapy has an immediate protective effect. It maintains functional activity of the injured nerve for a long period, decreases scar tissue formation at the injury site, decreases degeneration in corresponding motor neurons of the spinal cord, and significantly increases axonal growth and myelinization. In cell cultures, laser irradiation accelerates migration, nerve cell growth, and fiber sprouting. In a pilot, clinical, double‐blind, placebo‐controlled randomized study in patients with incomplete long‐term peripheral nerve injury, 780‐nm laser irradiation can progressively improve peripheral nerve function, which leads to significant functional recovery. A 780‐nm laser phototherapy temporarily preserves the function of a denervated muscle, and accelerates and enhances axonal growth and regeneration after peripheral nerve injury or reconstructive procedures. Laser activation of nerve cells, their growth, and axonal sprouting can be considered as potential treatment for neural injury. Animal and clinical studies show the promoting action of phototherapy on peripheral nerve regeneration, which makes it possible to suggest that the time for broader clinical trials has come. [Copyright &y& Elsevier]

Translation of laboratory results to the patient is a critical step in biomedical research and sometimes promising basic science and preclinical results fail to meet the expectations when translated to the clinics. End‐to‐side (ETS) nerve regeneration is an example of an innovative neurobiological concept, which, after having generated great expectations in experimental and preclinical studies, provided very conflicting results when applied to clinical case series. A number of basic science studies have shown that ETS neurorrhaphy, in fact, is able to induce collateral sprouting from donor nerve''s axons, allowing for massive repopulation of the distal nerve stump. Experimental studies have also shown that ETS neurorrhaphy can recover voluntary control of skeletal muscles and that voluntary motor function recovery can be achieved both with agonistic and antagonistic donor nerves, thus widening the potential clinical indications. However, clinical case series reported so far, did not meet these promises and results have been rather conflicting, especially regarding repair of proximally located mixed nerves. In contrast, ETS reconstruction of distal sensory nerve lesions led to a more positive outcome and, most importantly, consistent results among international centers carrying out clinical trials. Concluding, ETS is a promising microsurgical approach for nerve coaptation, based on a convincing and innovative neurobiological concept. However, conflicting clinical results and disagreement among surgeons regarding its employment suggest that this technique should still be considered an ultima ratio, reserved for cases where no other repair technique can be attempted. New data coming from neurobiological research will help further enlarge the clinical indications of ETS nerve reconstruction, explain the different results found in laboratory animals and humans, and contribute to new treatments and rehabilitation strategies aimed at improving the efficacy of nerve regeneration after ETS neurorrhaphy. [Copyright &y& Elsevier]

Tissue engineering of peripheral nerves has seen an increasing interest over the last years and, similarly to many other fields of regenerative medicine, great expectations have risen within the general public to its potential clinical application in the treatment of damaged nerves. However, in spite of the scientific advancements, applications to the patients is still very limited and it appears that to optimize the strategy for the tissue engineering of the peripheral nerves in the clinical view, researchers have to strive for a new level of innovation which will bring together (in a multitranslational approach) the main pillars of tissue engineering: namely (1) microsurgery, (2) cell and tissue transplantation, (3) material science, and (4) gene transfer. This review paper provides an overview of these four key approaches to peripheral nerve tissue engineering. While some of these issues will also be specifically addressed in other papers in this special issue on peripheral nerve regeneration of the International Review of Neurobiology, in this paper we will focus on an example of successful translational research in tissue engineering, namely nerve reconstruction by muscle–vein‐combined nerve scaffolds. [Copyright &y& Elsevier]

This paper critically overviews the main procedures used for carrying out morphological analysis of peripheral nerve fibers in light, confocal, and electron microscopy. In particular, this paper emphasizes the importance of osmium tetroxide post‐fixation as a useful procedure to be adopted independently from the embedding medium. In order to facilitate the use of any described techniques, all protocols are presented in full details. The pros and cons for each method are critically addressed and practical indications on the different imaging approaches are reported. Moreover, the basic rules of morpho‐quantitative stereological analysis of nerve fibers are described addressing the important concepts of design‐based sampling and the disector. Finally, a comparison of stereological analysis on myelinated nerve fibers between paraffin‐ and resin‐embedded rat radial nerves is reported showing that different embedding procedures might influence the distribution of size parameters. [Copyright &y& Elsevier]

This paper addresses several basic issues that are important for the experimental model design to investigate peripheral nerve regeneration. First, the importance of carrying out adequate preliminary in vitro investigation is emphasized in light of the ethical issues and with particular emphasis on the concept of the Three Rs (Replacement, Reduction, and Refinement) for limiting in vivo animal studies. Second, the various options for the selection of the animal species for nerve regeneration research are reviewed. Third, the two main experimental paradigms of nerve lesion (axonotmesis vs. neurotmesis followed by microsurgical reconstruction) are critically outlined and compared. Fourth, the various nerve models that have most commonly been employed are overviewed focusing in particular on forearm mixed nerves and on behavioural tests for assessing their function: the ulnar test and the grasping test which is useful for assessing both median and radial nerves in the rat. Finally, the importance of considering the influence of various factors and diseases which could interfere with the nerve regeneration process is emphasized in the perspective of a wider adoption of experimental models which more closely mimic the environmental and clinical conditions found in patients. [Copyright &y& Elsevier]

Peripheral nerves are complex organs that can be found throughout the body reaching almost all tissues and organs to provide motor and/or sensory innervation. A parenchyma (the noble component made by the nerve fibers, i.e., axons and Schwann cells) and a stroma (the scaffold made of various connective elements) can be recognized. Although morphological analysis is the most common approach for studying peripheral nerve regeneration, researchers are not always aware of several histological peculiarities of these organs. Therefore, the aim of this review is to describe, at a structural and ultrastructural level, the main features of the parenchyma and the stroma of the normal undamaged nerve as well as the most important morphological changes that occur after nerve damage and during posttraumatic nerve regeneration. The paper is aimed at providing the reader with the basic framework information on nerve morphology. This would enable the correct interpretation of morphological data obtained by many experimental studies on peripheral nerve repair and regeneration such as those outlined in several other papers included in this special issue of the International Review of Neurobiology. [Copyright &y& Elsevier]

Although the most significant advances in nerve repair and regeneration have been acquired over the last few decades, the study of nerve repair and regeneration potential dates back to ancient times namely to Galen in the second century A.D. This brief historical note outlines the milestones which have guided us to our present knowledge. In particular, we focus on the nineteenth century and the first decades of the twentieth century, an age in which the fathers of neurosurgery and neurobiology established the basis for most of the nerve repair and regeneration concepts used today. Finally, we shine a light on the most current history to show how recent pressure to use modern interdisciplinary and translational approach represents a sort of rediscovery of the scientific habits of the fathers of modern biomedicine, who used to carry out research from an integrated and broad point of view rather than from a super‐specialized and specific one as it is often used today. [Copyright &y& Elsevier]

Abstract: The last 15 years have seen a growing interest regarding a technique for nerve repair named end-to-side (terminolateral) neurorrhaphy. This technique is based on the concept that nerve fiber regeneration along the distal stump of a transected nerve, the proximal stump of which was lost, can be obtained by just suturing the proximal end of its distal stump to the epinerium of a neighbor healthy and undamaged donor nerve. A large body of experimental studies have shown that end-to-side neurorrhaphy, in fact, is able to induce collateral sprouting from donor nerve''s axons which is at the basis of the massive repopulation of the distal nerve stump. The regenerating nerve fibers eventually reinnervate the periphery of the severed nerve leading to a recovery of the lost function the degree of which varies depending on factors that still have to be elucidated. Surprisingly, this puzzling concept of nerve regeneration has attracted very little attention from basic neuroscientists so far and, thus, the present paper is intended to call for more biological research on it by overviewing the relevant literature and indicating the several unanswered questions that this concept asks to the neuroscience community. [Copyright &y& Elsevier]

Presents a debate over stereological methods of counting neural structures. Definition of an optical dissector; Cost-effectiveness of three-dimensional cell counting; Validity of stereological methods.

Highlights • Several methods have been developed to analyze locomotion in the rat model after SCI. • Kinematic parameters can allow detection of subtle deficits in gait following SCI. • With ground reaction forces it is possible to identify gait compensatory mechanisms. • The use of multiple kinematic and kinetic parameters is crucial for future studies. Abstract 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. [ABSTRACT FROM AUTHOR]

Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating is the disruption of the ability to perform functional movement. Very little is known on the recovery of hindlimb joint kinematics after clinically-relevant contusive thoracic lesion in experimental animal models. A new functional assessment instrument, the dynamic feet distance (DFD) was used to describe the distance between the two feet throughout the gait cycle in normal and affected rodents. The purpose of this investigation was the evaluation and characterization of the DFD during treadmill locomotion in normal and T9 contusion injured rats, using three-dimensional (3D) instrumented gait analysis. Despite that normal and injured rats showed a similar pattern in the fifth metatarsal head joints distance excursion, we found a significantly wider distance between the feet during the entire gait cycle following spinal injury. This is the first study to quantify the distance between the two feet, throughout the gait cycle, and the biomechanical adjustments made between limbs in laboratory rodents after nervous system injury. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a widespread and disabling condition that can impair the individual’s daily life. Studies involving medications that may positively affect peripheral nerve regeneration are rare. The aim of this study was to investigate new treatments after peripheral nerve injury using various neuroprotectants, melatonin, alcar and leptin, in the regenerative process in an experimental rat model. Wistar albino rats were randomly divided into eight groups containing equal number of animals. Intraperitoneal injection of melatonin (50 mg/kg, for 21 days), leptin (1 mg/kg, for 21 days) and acetyl- l -carnitine (50 mg/kg, for six weeks) was performed postoperatively. Histological and electromyographical assessments of the regenerated nerves were performed 12 weeks after surgery. Stereological analysis was performed to estimate myelinated and unmyelinated axon numbers, surface area, myelin thickness and the myelin thickness/axon diameter ratio for each group. The results showed that only alcar has a beneficial effect on the regeneration of unmyelinated axons. Neither melatonin and leptin nor alcar were observed to have any therapeutic effect on the regeneration of myelinated axons. Alcar therapy has a positive effect on the regeneration of unmyelinated fiber in the sciatic nerve. However, the same effect was not observed in myelinated nerve fibers after intraperitoneal application of melatonin and leptin. [ABSTRACT FROM AUTHOR]

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. [ABSTRACT FROM AUTHOR]

Background Perineural fibrotic adhesions are among the major complications of peripheral nerve surgery. While different experimental models have been used for the pre-clinical testing of anti-adherential strategies, the methods used so far to induce scar tissue appear to be poorly standardized and reproducible. New method Thirty adult mice were used. Two methods were tested: the first one is based on burning the perineural muscular bed with a diathermocoagulator, while the second is based on direct scratching of the nerve surface with a cotton swab. After 3 weeks, the fibrotic reaction was assessed by measuring the peak pull out force of the nerve from muscular bed by means of a new tool specifically devised for biomechanical assessment of scar tissue formation. Moreover, histological analysis with specific collagen stain was also carried out. Results Both methods produced fibrotic reaction. Statistical analysis of biomechanical data showed a significant difference between burning and scratching group compared to the control sham operated group. No significant differences were detected between burning and scratching group. Histological analysis showed the presence of perineural scar tissue in both groups, though with a different distribution pattern. Comparison with other methods This protocol is easier to perform. The tool used for biomechanical evaluation is reliable and cheap. Conclusions Both methods for perineural scar formation are effective and simple. They represent reproducible models for the study of the anti-adherential strategies. Yet, biomechanical testing with the device that we have developed proved to be a reliable and simple method for the quantitative assessment of the degree of perineural adhesion formation. [ABSTRACT FROM AUTHOR]

Abstract: Numerous animal model studies in the past decade have demonstrated that pharmacological elevation of cyclic AMP (cAMP) alone, or in combination with other treatments, can promote axonal regeneration after spinal cord injury. Elevation of cAMP via the phosphodiesterase 4 (PDE4) inhibitor, rolipram, decreases neuronal sensitivity to myelin inhibitors, increases growth potential and is neuroprotective. Rolipram''s ability to cross the blood–brain barrier makes it a practical and promising treatment for CNS regeneration. However, several studies have questioned the efficacy of rolipram when given alone. The purpose of this investigation was to determine the effects of continuous administration of rolipram, given alone for 2 weeks, following a moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale and the beam walk. We used three-dimensional (3D) instrumented gait analysis to allow detailed assessment and quantification of hindlimb motion. The amount of the damaged tissue and spared white matter was estimated stereologically. Our results show that administration of rolipram following acute spinal cord contusion results in improved motor performance at each time-point. Dynamic assessment of foot motion during treadmill walking revealed a significantly decreased external rotation during the entire step cycle after 8 weeks in rolipram-treated animals. Stereological analysis revealed no significant differences in lesion volume and length. By contrast, spared white matter was significantly higher in the group treated with rolipram. Our results suggest a therapeutic role for rolipram delivered alone following acute SCI. [Copyright &y& Elsevier]

Abstract: Cell transplantation therapy has raised a great interest in the perspective of its employment for nerve tissue repair. Among the various cell populations proposed, olfactory ensheathing glial cells have raised great interest over recent years, especially in the perspective of their employment for neural repair because of their homing capacity in both central and peripheral nervous system. This paper is aimed to provide an in vitro characterization of the NOBEC (neonatal olfactory bulb ensheathing cell) line that was obtained from primary cells dissociated from rat neonatal olfactory bulb (OB) and immortalized by retroviral transduction of SV40 large T antigen. Light and electron microscopy investigation showed that NOBECs are a homogeneous cell population both at structural and ultrastructural level. RT-PCR, Western blotting and immunocytochemistry showed that NOBECs express the glial markers S100, GFAP (Glial Fibrillar Acid Protein) and p75NGFR as well as NRG1 (neuregulin-1) and ErbB1-2-3 receptors; while they are negative for ErbB4. Yet, NOBECs exhibit a high proliferation and migration basal activity and can be transducted with vectors carrying GFP (green fluorescent protein) and NRG1 cDNA. Functional stimulation by means of NRG1-III-β3 overexpression through viral transduction induced a significant increase in cell proliferation rate while it had no effect on cell migration. Altogether, these results show that NOBEC cell line retain glial features both morphologically and functionally, responding to the NRG1/ErbB-mediated gliotrophic stimulus, and represents thus a good tool for in vitro assays of glial cell manipulation and for in vivo experimental studies of glial cell transplantation in the central and peripheral nervous system. [Copyright &y& Elsevier]

Abstract: Postconditioning (PostC) may limit mitochondrial damage and apoptotic signaling. We studied markers of apoptosis and mitochondrial protection in isolated rat hearts, which underwent a) perfusion without ischemia (Sham), b) 30-min ischemia (I) plus 2-hour reperfusion (R), or c) PostC protocol (5 intermittent cycles of 10-s reperfusion and 10-s ischemia immediately after the 30-min ischemia). Markers were studied in cytosolic (CF) and/or mitochondrial (MF) fractions. In CF, while pro-apoptotic factors (cytochrome c and caspase-3) were reduced, the anti-apoptotic markers (Bcl-2 and Pim-1) were increased by PostC, compared to the I/R group. Accordingly, phospho-GSK-3β and Bcl-2 levels increased in mitochondria of PostC group. Moreover, I/R reduced the level of mitochondrial structural protein (HSP-60) in MF and increased in CF, thus suggesting mitochondrial damage and HSP-60 release in cytosol, which were prevented by PostC. Electron microscopy confirmed that I/R markedly damaged cristae and mitochondrial membranes; damage was markedly reduced by PostC. Finally, total connexin-43 (Cx43) levels were reduced in the CF of the I/R group, whereas phospho-Cx43 level resulted in higher levels in the MF of the I/R group than the Sham group. PostC limited the I/R-induced increase of mitochondrial phospho-Cx43. Data suggest that PostC i) increases the levels of anti-apoptotic markers, including the cardioprotective kinase Pim-1, ii) decreases the pro-apoptotic markers, e.g. cytochrome c, iii) preserves the mitochondrial structure, and iv) limits the migration of phospho-Cx43 to mitochondria. [Copyright &y& Elsevier]

Abstract: Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating effects is the disruption of the ability to walk. Therefore, much effort has been focused on developing several methods to document the recovery of locomotor function after experimental SCI. Computerized rat gait analysis is becoming increasingly popular in the SCI research community. The two-dimensional (2D) kinematic approach is by far the most popular technique in rat gait analysis. This is a simple inexpensive procedure, which requires only one camera to record the movement. Our study included an examination of locomotion on a treadmill using 2D and three-dimensional (3D) analysis, in neurologically intact animals and following moderate T9 contusion injury. Despite the overall time course patterns of the curves were identical, we found significant differences between values of the 2D and 3D joint angular motion. In conclusion, maximal precision and accuracy of the kinematic values are expected when the experimental protocol includes a 3D motion analysis methodology. Moreover, a 2D method cannot be used to determine the external or internal rotations of the foot because this movement occurs in the transverse plane. [Copyright &y& Elsevier]

Abstract: The convenience of the motor-driven treadmill makes it an attractive instrument for investigating rat locomotion. However, no data are available to indicate whether hindlimb treadmill kinematic findings may be compared or generalized to overground locomotion. In this investigation, we compared overground and treadmill locomotion for differences in the two-dimensional angular kinematics and temporal and spatial measurements for the hindlimb. Ten female rats were evaluated at the same speed for natural overground and treadmill walking. The walking velocity, swing duration and stride length were statistically indistinguishable between the two testing conditions. Significant differences were found between overground and treadmill locomotion for step cycle duration and stance phase duration parameters. During the stance phase of walking, the angular movement of the hip, knee and ankle joints were significantly different in the two conditions, with greater flexion occurring on the overground. Despite this, the sagittal joint movements of the hindlimb were similar between the two walking conditions, with only three parameters being significantly different in the swing. Hip height and angle–angle cyclograms were also only found to display subtle differences. This study suggests that reliable kinematic measurements can be obtained from the treadmill gait analysis in rats. [Copyright &y& Elsevier]

Abstract: The assessment of recovery of the neuromuscular function following nerve lesion and repair is one of the main goals of peripheral nerve researchers. The forelimb model has recently seen an increase in its employment for experimental nerve repair studies especially because of the availability of the grasping test for assessing the functional recovery of one of its major nerves, the median nerve. Nerve repair studies sometimes require the use of more than one nerve to simulate severe clinical situations and, in this case, the ulnar nerve is often used together with the median nerve. However, a test for assessing ulnar nerve functional recovery is yet not available. To fill this gap, we have developed and experimentally tested a method for the functional assessment of posttraumatic ulnar nerve recovery in the rat. Animal testing using this method is simple, quick and provides the animal with minimal distress. The method proved to be effective in detecting the date on which recovery starts after ulnar nerve impairment and in following its improvement, over time. The availability of this new test is expected to further increase the employment of forelimb experimental nerve models instead of the more disabling hindlimb models. [Copyright &y& Elsevier]

The quantitative assessment of motor function is an important requirement for studies on peripheral nerve injury and repair. So far, most studies on peripheral nerves have been performed on the sciatic nerve model using walking track analysis for assessing motor function. Alternatively, the employment of the median nerve model, which allows motor function evaluation by means of a simple behavioural test named grasping test (GT), have been more recently proposed. In this paper, the efficacy of the GT for the quantitative assessment of motor function recovery is re-appraised and a modified device for its carrying out is described. Finally, the rationale for the employment of the median nerve model as an alternative to the sciatic nerve model is critically discussed. [Copyright &y& Elsevier]