The tasks of the study were as follows: to investigate histological findings of the spinal cord two hours after a trauma; to investigate the influence of the narrowing of spinal canal on the histological changes development of the injured spinal cord; to estimate the influence of the spinal cord surgical decompression performed within twenty hours after the cervical spine trauma on its clinical signs of the changes of the injury; to determinate the relationship between the duration of the cervical spinal cord compression and its clinical signs of changes of the injury. The main results: The hemorrhages in the gray matter and within the perivascular spaces of the spinal cord and beneath it dura mater, blood stasis in the vessels of the spinal cord gray matter and the thrombosis of the superficial spinal cord vessels, ischemic neurons were established in axial sections of the spinal cord two hours after the experimental trauma. The degree of pericellular edema established in axial sections of the spinal cord stained with hematoxylin and eosin by light microscopy two hours after the experimental trauma was more severe for the laboratory animals which underwent reduction of vertical diameter of the spinal canal by 50 % followed by spinal cord compression. The cervical spinal cord decompression performed within twenty four hours after trauma provided significant neurologic recovery twelve months after surgical intervention. The decompression of the injured spinal cord manifested... [to full text]

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<p>The World Health Organisation estimates that the majority of the disabled population resides in the developing world, but most of the research on outcomes of patients originates from the developed world. In the light of the differences in healthcare structures and function, especially rehabilitation between settings and countries, it is imperative to have an understanding of the&nbsp / functioning of patients at discharge with the objective of measuring the level at which outcomes are met. The aim of this study was therefore to determine the process of rehabilitation and the&nbsp / outcome of patients following in-patient rehabilitation at a facility in the Western Cape. A quantitative research design was employed to address the objectives. Self-administered&nbsp / questionnaires were developed to collate information pertaining to the demographic-, socioeconomic- and medical profile of patients and data extraction sheets collected information relating&nbsp / to the process of rehabilitation and the impairment status of patients on admission. With regards to activity and participation, a longitudinal study design was used, which utilised standardised&nbsp / outcomes measures. The sample consisted of all patients with stroke and spinal cord injury admitted within a three-month period, and all ethical principles relating to research on human&nbsp / subjects, as stipulated in the Helsinki Declaration were adhered to during data collection, with ethical clearance obtained from relevant authorities. The SAS and the Microsoft Excel Package&nbsp / 2007 were used to analyse the quantitative data elements. Descriptive statistics using frequencies, percentages, ranges, means, and standard deviations and inferential statistics using&nbsp / chi-square, student T-tests and correlation tests, for determining the predictors of functional outcome, were calculated. There were 175 patients, whereof 82 were patients with stroke and 93&nbsp / with spinal cord injury, with 143 (76 presenting with spinal cord injury and 67 with stroke) meeting the inclusion criteria on admission. The mean age of those with spinal cord injury and stroke&nbsp / was 34.14 and 52.95 years. Most of the patients with spinal cord injuries were single (73.68%), whereas the majority (53.73%) of patients with strokes were married at the time of injury. All&nbsp / patients were managed by the doctor and the nurse, with most of the patients receiving physiotherapy, occupational therapy and social assistance from the social worker. With regards to recreational activities, 46.87% of patients with spinal cord injury and 39.39% of those with stroke attended the learn to swim programme, and 29.68% of patients with spinal cord injury attended the wheelchair basketball sessions. The mean length of hospital stay for patients with spinal cord injury and stroke was 73.11 and 51. 62 days, with most of the spinal cord injured patients&nbsp / (80.26%) and stroke patients (82.08%) discharged home without follow-up rehabilitation. The most prevalent impairments on admission of the spinal cord injury cohort were muscle&nbsp / weakness (75.0%), bladder incontinence (71.1%) and reduced sensation (69.7%), whereas patients with stroke presented mostly with muscle paralysis (80.6%), abnormal tone (76.1%) and aphasia (50.8%). Functional limitations experienced by the participants included, mobility, stair climbing and transfers. The participants experienced participation restrictions in the following&nbsp / domains, leisure activities and employment. A clinical significant improvement was noted in execution of functional task of patients with spinal cord injury (p&lt / 0.0001) and stroke (p&lt / 0.0001)&nbsp / between admission and discharge. A significant statistical change was also detected for the participation elements of both stroke and spinal cord injury cohorts. Functional ability on&nbsp / admission was found to be a predictor of functional outcome of the stroke diagnostic group at discharge, whereas the multiple&nbsp / redictor model of functional outcome of the spinal cord injured cohort at discharge was significant with remaining variables of functional outcome score on admission (p&lt / 0.0001) and bladder -and bowel impairment(s) (p=0.0247). The study findings suggest that despite the significant change in activity and participation, most of the patients were discharged home without further follow-up for rehabilitation, irrespective of the activity&nbsp / limitations and participation restrictions still experienced at the time of discharge. The latter finding&nbsp / questions the duration of the length of hospital stay, which does not allow patients to be independent in all meaningful activities and participatory actions and roles by the end of inpatient rehabilitation. The study findings could assist authorities to adapt the existing rehabilitation&nbsp / programme and referral process . </p>

L’administration systémique d’atorvastatine s’est montrée neuroprotective suivant un traumatisme médullaire, en diminuant la réponse inflammatoire au site de la lésion ainsi qu’en réduisant l’apoptose des oligodendrocytes. Ce dernier épargne la matière blanche au site de l’insulte et améliore la locomotion. Le but de cette étude était de confirmer l’efficacité neuroprotective de l’atorvastatine ainsi que son action précoce, lorsqu’administré post-trauma, sur la limitation de l’apoptose. Des rats Sprague-Dawley femelles ont reçu une injection intrapéritonéale de : (1) statine/saline (5 mg/kg) 2 h après une lésion contusive; (2) saline physiologique 2 h post-contusion; ou (3) saline physiologique sans lésion. Les rats traités à la statine ont montré une amélioration significative (p<0.05) de leur locomotion après 4 semaines post-trauma, comparée au groupe « véhicule » lésé. Expliquant cette observation, l’activité de la caspase-3 fut diminuée de 50% (p<0.05) et la méthode de TUNEL révéla une diminution d’approximativement 20% du nombre de cellules apoptotiques au site lésionnel (p<0.01) 4 h après l’insulte contusive chez le groupe traité en comparaison aux groupes « véhicules ». Ces résultats démontrent que l’atorvastatine est efficace dans la prévention de l’apoptose précoce au site lésionnel dans un modèle expérimental de traumatisme médullaire après seulement 2 h post-traumatisme. / The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5 mg/kg) at 2 h after the contusion injury; (2) physiological saline at 2 h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p<0.05) improvement in locomotion at week 4 post-SCI compared to vehicle-treated animals. Explaining this outcome, caspase-3 activity decreased by 50% (p<0.05), and the histological TUNEL method revealed a decrease of approximately 20% in apoptotic cells at the injury site (p<0.01) at 4 h post-SCI in atorvastatin-treated rats in comparison to vehicle-treated controls. These data demonstrate that atorvastatin is effective after experimental spinal cord contusion injury in preventing early apoptosis at the injury site within 2 h post-administration.

Neurons in the spinal cord do not spontaneously regenerate, which often leads to debilitating injuries. One method proposed to promote axonal regeneration is the injection of viruses carrying genes for growth factors into the injured spinal cord. One such virus, the adeno-associated virus (AAV), has shown promise in gene therapy medical research. However, injecting AAV into rhesus macaques with C7 spinal cord hemisection lesions actually leads to motor neuron loss in the gray matter of the spinal cord, rather than contributing to the preservation or regeneration of axons. This unexpected result highlights the necessity of further testing with therapeutic approaches for axon regeneration in nonhuman primate models before moving into clinical trials. It is possible that an immune-related T cell response to the AAV-transfected cells causes this motor neuron loss. T cells are white blood cells that play a role in attacking cells infected with viruses. It is unknown whether such a response of the immune system to respond with an up-regulation of T cells may be taking place over a relatively short period (weeks) or over many months. This question was tested here: T cells were stained in spinal cord sections caudal (below) the lesion in the spinal cord and near AAV injection sites to determine whether there was a greater quantity of T cells in these areas compared to the subject’s baseline levels. Subjects that had AAV therapeutic injections and that were examined 6 months after the injection were found to have greater quantities of T cells than those who did not have injections containing AAV. It was also found that the AAV-injected subjects examined only 6 weeks post injection did not have greater quantities of T cells than control subjects. These results suggest that there may be a delayed immune response to the AAV injections in nonhuman primates with spinal cord injury, which occurs over a period of months. Pinpointing the mechanism that causes this cell death would allow researchers to create a safer therapeutic that could promote axonal growth in people with spinal cord injuries.

There is an unmet medical need for the efficient treatment of neuropathic pain, a condition that affects approximately 10% of the population worldwide. Current therapies need to be improved due to the associated side effects and lack of response in many patients. Moreover, neuropathic pain causes great suffering to patients and puts an economical burden on society. The work presented in this thesis addresses SP1-7, (Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), a major metabolite of the pronociceptive neuropeptide Substance P (SP). SP is released in the spinal cord following a noxious stimulus and binds to the NK1 receptor. In contrast to SP, the degradation fragment SP1-7 is antinociceptive through binding to specific binding sites distinct from the NK1 receptor. The aim of this thesis was to investigate the impact of SP1-7 on neuropathic pain. To understand how SP1-7 exerts its effect, a series of N-truncated forms of the heptapeptide were biologically evaluated. A set of small high-affinity ligands was evaluated in animal models of neuropathic pain. To confirm a clinical relevance the levels of SP1-7 in human neuropathic pain were assessed incerebrospinal fluid (CSF) collected from neuropathic pain patients. The results showed that SP1-7 could alleviate thermal as well as mechanical hypersensitivity in three different animal models of neuropathic pain. C-terminal amidation was connected with increased efficacy. N-terminal truncation of SP1-7 indicated a necessity of five amino acids in order to retain biological effect. One small high-affinity ligand showed a significant anti-allodynic effect. CSF levels of SP1-7 in neuropathic pain patients were lower compared to controls. Taken together, these findings demonstrate that the formation of SP1-7 may be attenuated in neuropathic pain. C-terminal amidation and a majority of its amino acids are necessary for stability and permeability. Clearly, SP1-7 and SP1-7 mimetics with high affinity to the SP1-7 binding site ameliorate neuropathic pain-like behaviors in animal models of neuropathic pain. Overall, the findings presented in this thesis contribute to new knowledge regarding the role of SP1-7 and related analogues and fragments in neuropathic pain. In a future perspective, this could be essential for the development of efficient strategies for managing patients with neuropathic pain.

Conventional functional electrical stimulation (FES) therapy, if provided shortly after an incomplete spinal cord injury, is able to help an individual to restore voluntary hand function. This is thought to occur through the induction of neuroplasticity. However, conventional FES therapy employs a push-button-based control scheme, which does not fully require the recipient to generate volitional movements. The first study in this thesis therefore sought to determine, in an early proof-of-concept test with able-bodied participants, whether control strategies which are triggered by volitional activity (including an electroencephalography-based brain-machine interface (BMI-FES) and an electromyogram-based control scheme (EMG-FES)) might provide greater benefits to hand function. The results offer relatively weak evidence to suggest that BMI-FES, and especially EMG-FES, were able to induce greater neuroplasticity than conventional treatments in the corticospinal tract leading to the hands, but that this did not immediately translate to more functional improvements such as maximum grip force. ii The second study in this thesis focussed on spinal associative stimulation (SAS), which involves paired stimulation pulses at both the head (via transcranial magnetic stimulation), and the wrist (via peripheral nerve stimulation). The purpose of this, as with the first study, was to induce neuroplasticity and upregulate the corticospinal tract leading to the hands. While limited research has suggested that it is possible to produce neuroplasticity through SAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz. The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz “bursts”. None of the paradigms were able to successfully induce neuroplasticity in a consistent manner. The increased variability in this study as compared to the previous one, despite the nearly identical assessment methodology, suggests that responses to the SAS treatment may have been highly individual. This serves to highlight a potential limitation of the treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by SAS should it continue to be tested as a novel therapy.

Although spinal cord injury (SCI) is a debilitating condition that presents a large socioeconomic problem in the United States, there is currently no treatment that reliably reduces morbidity and mortality. Current research is aimed at identifying mechanisms involved in the pathophysiology of SCI and using this knowledge to develop rational treatments. We have observed plasma membrane compromise in the acute (within 10 minutes), sub-acute (3 days), and chronic phases (5 weeks) in a rat model of contusion SCI and postulate that it negatively affects neurological outcome. Holes/tears in the plasma membrane were assessed with a dye exclusion assay, in which a fluorescent cell-impermeant dye was injected into the cerebrospinal fluid prior to sacrifice; therefore, cellular uptake of the dye is indicative of plasma membrane compromise. As early as 10 minutes after SCI, widespread uptake of permeability markers was evident in neuronal cell bodies as well as axonal projections. The number of permeable cells and the size of the membrane breaches (measured by using permeability markers of various sizes) varied with distance from the injury site, with larger disruptions located closer to the epicenter. Greater cellular uptake was observed when the impact force was increased (200 > 150 > 100 kdyn > sham). At longer time points (3 days and 5 weeks), substantial permeability marker uptake was observed in axons but not in cell bodies. Cells with increased permeability displayed a variety of pathomorphological alterations, including swelling, blebbing, retraction bulb formation, neurofilament loss, and fragmentation, suggesting that increased plasma membrane permeability is detrimental to cell survival and function. We therefore investigated a clinically-relevant treatment strategy designed to restore plasma membrane integrity. Animals were treated with citicoline, a molecule utilized in the endogenous synthesis of phosphatidylcholine (the major membrane component in mammalian cells). Citicoline has been shown to be beneficial in numerous studies of neurological disease, improving overall outcome by increasing phospholipid synthesis and attenuating phospholipid destruction (by reducing phospholipase A2 activity). However, these mechanisms have not been explored in a model of SCI. When compared to injured animals receiving vehicle (saline) injections, citicoline treatment after SCI did not have a statistically significant effect on cytoplasmic PLA2 activity (at 24h post-injury), the density of permeable axons (at 3 days post-injury), or the lesion volume (at 3 days post-injury). Since citicoline may improve neurological outcome after SCI through mechanisms we did not directly assess, we then conducted a longer-term study to evaluate the overall efficacy of citicoline treatment in terms of longer-term functional and histological consequences. Citicoline did not have a biologically significant effect on behavioral recovery (evaluated during open field locomotion, grid walk and hyperalgesia testing weekly for up to 5 weeks post-injury) or lesion volume (at 5 weeks post-injury). The lack of citicoline-mediated effect may be attributed to experimental parameters (e.g., dosing or sensitivity of outcome measures) or biological inefficacy. Although we were not able to demonstrate that citicoline improves outcome after SCI, the finding that plasma membrane damage occurs in a persistent fashion and is associated with pathophysiological cellular alterations may provide fundamental knowledge necessary for developing treatments targeted at membrane repair. Future work examining the complex mechanisms causing prolonged membrane damage after SCI and evaluating strategies for manipulating these pathways (potentially using citicoline in combination with other pharmacological agents) may lead to a clinically effective therapy.

O objetivo desta Tese foi analisar os efeitos do treino de marcha isolado e em combinação com transplante de glia embainhante olfatória (GEO) na recuperação funcional e na plasticidade neuromuscular dependente da atividade em um modelo experimental de paraplegia. Para tanto, foram realizados 2 experimentos. No 1º experimento foi realizada completa transecção da medula espinal (TME) em ratos Wistar adultos e após 5 dias iniciou-se um protocolo de 9 semanas de treino de marcha em esteira com suporte de peso corporal. No 2º experimento, os animais receberam, imediatamente após a TME, transplante de células gliais embainhantes olfatórias (GEO) e, como no primeiro experimento, iniciaram o treino de marcha 5 dias após a lesão/transplante. Durante o período dos experimentos, estudos comportamentais para acompanhamento da recuperação da função sensório-motora dos animais foram periodicamente realizados. Além disso, ao término da fase de treinamento (10 semanas após a lesão/transplante), análises histológicas e bioquímicas foram realizadas em amostras de tecido retiradas da medula espinal e músculo sóleo. Os resultados mostram que o treino de marcha em esteira promove melhora da função sensório-motora nos membros posteriores (MPs) de ratos com completa transecção da medula espinal (TME). Os animais treinados apresentaram escores mais altos na escala BBB e normalização do reflexo flexor de retirada. Além disso, os animais com TME apresentaram atrofia do soma celular nos motoneurônios alfa, redução na expressão de sinaptofisina e na atividade da Na+,K+-ATPase na região lombar. Os animais treinados mostraram soma motoneuronal, expressão de sinaptofisina e atividade da bomba de Na+,K+-ATPase similares aos controles. No músculo sóleo, a TME causou severa atrofia muscular, que foi acompanhada pela redução na expressão do fator neurotrófico derivado do encéfalo (BDNF) neste músculo. Por outro lado, o treino de marcha foi capaz de parcialmente impedir/reverter a atrofia provocada pela paralisia muscular e promover um significante aumento na expressão do BDNF, o qual teve positiva correlação com o trofismo muscular dependente da atividade motora no músculo sóleo. O transplante de glia embainhante olfatória (GEO) promoveu significativo aumento nos escores da escala BBB nos animais com completa TME. Entretanto, o treino de marcha foi capaz de acelerar este ganho funcional. Apesar de não ser observada significativa regeneração axonal através do local da lesão, sugerindo que as melhoras funcionais ocorreram independentemente da existência de regeneração axonal. Estes resultados sugerem que o treino de marcha após a TME promove plasticidade morfológica e bioquímica dependente da atividade nos tecidos neuromusculares. A melhora funcional ocorreu concomitantemente a estas alterações plásticas. Além disso, a terapia de transplante de GEO mostrou resultados positivos na recuperação da função motora dos MPs que foi acelerada pelo treino de marcha, mesmo na ausência de regeneração axonal através da lesão. Estes dados mostram importantes informações neurobiológicas que fornecem base neurocientífica para o uso seguro e eficaz destas terapias na reabilitação após LME. / The aim of this thesis was to study the effects of treadmill step training alone and in combination with olfactory ensheathing cells (OEC) on functional recovery and activity-dependent neuromuscular plasticity in a traumatic paraplegia model. For this, we made two experiments. In the 1st experiment, complete spinal cord transection (SCT) was made in adult Wistar rats and after 5 days the spinal animals were underwent a 9 week body-weight-supported treadmill training (BWSTT) program. In the 2nd experiment, the spinal animals received acute olfactory ensheathing cell (OEC) transplantation and, similar to the 1st experiment, started a BWSTT 5 days after the injury/transplantation. Behavioral tests were periodically performed in order to study the hindlimb sensorimotor functions in both experiments. Furthermore, after 9 weeks of the training (10 weeks after SCI/transplantation), histological and biochemical analysis were performed in spinal cord and soleus muscle tissues. The results show that treadmill step training improves hindlimb sensorimotor function in rats with complete spinal cord transection (SCT). The trained animals showed higher BBB scores and normalization of the withdrawal reflex. Furthermore, spinal animals showed alpha motoneuron soma size atrophy, decrease in synaptophysin expression and Na+,K+-ATPase activity in lumbar spinal cord. Trained SCT animals showed motoneuron soma size, synaptophysin expression and Na+,K+-ATPase activity values similar to controls. In soleus muscle, SCT led to severe muscular atrophy, which was accompanied by a decrease in brain-derived neurotrophic factor (BDNF) expression in this muscle. On the other hand, treadmill step training was able to revert/prevent this paralysis-induced muscular atrophy and promote significant improvement in soleus BDNF expression, which was positively correlated to activity-dependent muscular trophism. Olfactory ensheathing cell (OEC) transplantation promotes significant improvements in the BBB scores of animals with SCT. However, treadmill step training was able to accelerate this functional gain. There was no significant axonal regeneration that traversed the injury site, which suggests that functional gains occurred in a manner independent of axonal regeneration. Taken as a whole, these results suggest that treadmill step training after SCT promotes activity-dependent morphological and biochemical plasticity in neuromuscular tissues. The functional improvements occurred concomitantly to these plastic changes. Moreover, OEC therapy showed positive results on hindlimb motor function recovery which was accelerated with treadmill step training even in the absence of axonal regeneration across the lesion site. These results represent important neurobiological information for the neuroscientific basis that supports these therapies as an efficient and safe approach in spinal cord injury rehabilitation.

Lesões medulares resultam em uma perda irreversível da função abaixo do sítio da lesão. Esses comprometimentos são permanentes e ocorrem devido à perda de neurônios localmente e também dos tratos axonais ascendentes e descendentes da medula espinal. Na tentativa de criar um ambiente favorável à regeneração dos axônios lesionados, células da glia embainhante olfatória (GEO) vêm sendo transplantadas como estratégia de tratamento em animais submetidos a diferentes modelos experimentais de lesões medulares. Entretanto, um consenso sobre o potencial terapêutico desse tipo de transplante celular ainda precisa ser estabelecido. O objetivo do presente trabalho foi verificar a eficácia do transplante de lâmina própria (LP) olfatória (que possui células da GEO) e de LP respiratória (desprovido de células da GEO), quando implantadas imediatamente, 2 ou 4 semanas após a realização da transecção da medula espinal. Doze semanas após a realização dos implantes, os animais que receberam LP olfatória e respiratória apresentaram uma melhora sutil na função motora dos membros posteriores. Além disso, o transplante de LP olfatória quando realizado imediatamente após a lesão reduziu a hiperatividade do reflexo de retirada, enquanto o implante desse tipo de tecido 4 semanas pós-lesão produziu uma discreta depressão dependente de frequência do reflexo de Hoffman (um análogo elétrico do reflexo monossináptico de estiramento). Nas diferentes janelas terapêuticas utilizadas, o transplante de ambos os tipos de LP produziu resultados comparáveis em relação à preservação do tecido medular, brotamento de neuritos e regeneração de fibras mielínicas no local da lesão, indicando que o tempo decorrido antes da realização dos transplantes não parece limitar os efeitos regenerativos. Todavia, as fibras mielínicas observadas no sítio da transecção nos animais que receberam LP olfatória 2 e 4 semanas pós-lesão possuíam menor área, diâmetro e espessura da bainha de mielina quando comparados aos animais que receberam LP respiratória nesses mesmos períodos. O transplante imediato de LP olfatória e respiratória também favoreceu o restabelecimento das conexões entre as fibras axonais lesionadas com núcleos do tronco encefálico e até mesmo com a região do córtex somatossensorial, como indicado pela presença de neurônios nessas regiões marcados positivamente com um marcador axonal retrógrado. Um número maior de fibras positivas para 5-HT foi observado no coto proximal dos grupos transplantados com ambos os tipos de LP em comparação às regiões da lesão e do coto caudal. Fibras positivas para CGRP estavam presentes em número considerável no local da lesão. A recuperação locomotora e a regeneração axonal no local da lesão foram limitadas e comparáveis entre os grupos transplantados nos diferentes tempos com LP olfatória e respiratória, sugerindo que esses resultados não estão exclusivamente relacionados à presença de células da GEO nos enxertos utilizados. Um melhor entendimento sobre o potencial restaurativo desse tipo de transplante é necessário a fim de justificar a aplicação dessa terapia em humanos. / Spinal cord injury (SCI) results in an irreversible loss of function below the injury site. These permanent disabilities occur due to local neuronal death and loss of ascending and descending axons in the spinal cord. In attempt to create a favorable environment for the re-growth of injured axons, olfactory ensheathing cells (OECs) have been transplanted as a treatment strategy in animals submitted to different experimental models of SCI. However, a consensus on the efficacy of this cellular transplantation has yet to be reached. The main focus of the present study was explore the efficacy of olfactory lamina propria (OLP, graft containing OECs) or respiratory lamina propria (RLP, graft without OECs) when transplanted immediately, 2-week or 4-week after spinal cord transection. After 12 weeks of transplantation, animals with OLP and RLP grafts showed a subtle hindlimb motor improvement. Furthermore, the transplantation of OLP when performed immediately after injury reduced the withdrawal reflex over-responsiveness, while the implantation of this tissue 4 weeks post-injury produced a discrete frequency-dependent habituation of the Hoffman reflex (the electrical analogue of the classic tendon jerk reflex). In all therapeutic windows used, both lamina propria grafts produced comparable results for tissue sparing, fibers sprouting and re-growth of myelinated fibers at the lesion site, indicating that delayed transplantation approach does not seem to limit the regenerative effects. However, the myelinated fibers observed at the transection site of animals that received OLP 2 or 4 weeks after injury had a smaller myelinated fiber area, diameter and myelin sheath thickness when compared to those animals transplanted with RLP grafts in the same periods. The immediate transplantation of OLP and RLP also foster limited supraspinal axonal re-connection as shown by the presence of neurons stained by retrograde tracing in brainstem nuclei and in the somatosensory cortex. A larger number of 5-HT positive axons were found in the cranial stump of both lamina propria groups compared to the lesion and caudal regions. CGRP positive axons were present in considerable numbers at the SCI site. The locomotor recovery and axon reparative effects were limited and similar between groups transplanted at different times with OLP and RLP, suggesting that these results could not be exclusively related to OECs. In conclusion, a greater understanding of the restorative potential of these tissue grafts is necessary to strengthen the rationale for application of this treatment in humans.