RESUMO
The vascular and the nervous systems share similarities in addition to their complex role in providing oxygen and nutrients to all cells. Both are highly branched networks that frequently grow close to one another during development. Vascular patterning and neural wiring share families of guidance cues and receptors. Most recently, this relationship has been investigated in terms of peripheral nervous system (PNS) regeneration, where nerves and blood vessels often run in parallel so endothelial cells guide the formation of the Büngner bands which support axonal regeneration. Here, we characterized the vascular response in regenerative models of the central and peripheral nervous system. After sciatic nerve crush, followed by axon regeneration, there was a significant increase in the blood vessel density 7 days after injury. In addition, the optic nerve crush model was used to evaluate intrinsic regenerative potential activated with a combined treatment that stimulated retinal ganglion cells (RGCs) regrowth. We observed that a 2-fold change in the total number of blood vessels occurred 7 days after optic nerve crush compared to the uncrushed nerve. The difference increased up to a 2.7-fold change 2 weeks after the crush. Interestingly, we did not observe differences in the total number of blood vessels 2 weeks after crush, compared to animals that had received combined treatment for regeneration and controls. Therefore, the vascular characterization showed that the increase in vascular density was not related to the efficiency of both peripheral and central axonal regeneration.
Assuntos
Axônios , Regeneração Nervosa , Camundongos , Animais , Axônios/fisiologia , Regeneração Nervosa/fisiologia , Células Endoteliais , Nervo Óptico/fisiologia , Células Ganglionares da Retina/fisiologia , Compressão NervosaRESUMO
The pleiotropic role of the major histocompatibility complex class I (MHC-I) reflects the close association between the nervous and immune systems. In turn, MHC-I upregulation postinjury is associated with a better regenerative outcome in isogenic mice following peripheral nerve damage. In the present work, we compared the time course of neuronal, glial, and sensorimotor recovery (1, 3, 5, 7, and 28 days after lesiondal) following unilateral sciatic nerve crush in A/J and C57BL/6J mice. The A/J strain showed higher expression of MHC-I (7 dal, ** p < 0.01), Iba-1 (microglial reaction, 7 dal, *** p < 0.001), and GFAP (astrogliosis, 5 dal, * p < 0.05) than the C57BL/6J counterpart. Synaptic coverage (synaptophysin) was equivalent in both strains over time. In addition, mRNA expression of microdissected spinal motoneurons revealed an increase in cytoskeleton-associated molecules (cofilin, shp2, and crmp2, * p < 0.05), but not trkB, in C57BL/6J mice. Gait recovery, studied by the sciatic functional index, was faster in the A/J strain, despite the equivalent results of C57BL/6J at 28 days after injury. A similar recovery was also seen for the nociceptive threshold (von Frey test). Interestingly, when evaluating proprioceptive recovery, C57BL/6J animals showed an enlarged base of support, indicating abnormal ambulation postinjury. Overall, the present results reinforce the role of MHC-I expression in the plasticity of the nervous system following axotomy, which in turn correlates with the variable recovery capacity among strains of mice.
Assuntos
Nervo Isquiático , Medula Espinal , Camundongos , Animais , Camundongos Endogâmicos C57BL , Medula Espinal/metabolismo , Axotomia/métodos , Compressão Nervosa , Gliose/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Camundongos EndogâmicosRESUMO
Activating and inhibitory immune receptors play a critical role in regulating systemic and central nervous system (CNS) immune and inflammatory processes. The CD200R1 immunoreceptor induces a restraining signal modulating inflammation and phagocytosis in the CNS under different inflammatory conditions. However, it remains unknown whether CD200R1 has a role in modulating the inflammatory response after a peripheral nerve injury, an essential component of the successful regeneration. Expression of CD200R1 and its ligand CD200 was analyzed during homeostasis and after a sciatic nerve crush injury in C57Bl/6 mice. The role of CD200R1 in Wallerian Degeneration (WD) and nerve regeneration was studied using a specific antibody against CD200R1 injected into the nerve at the time of injury. We found an upregulation of CD200R1 mRNA after injury whereas CD200 was downregulated acutely after nerve injury. Blockade of CD200R1 significantly reduced the acute entrance of both neutrophils and monocytes from blood after nerve injury. When long term regeneration and functional recovery were evaluated, we found that blockade of CD200R1 had a significant effect impairing the spontaneous functional recovery. Taken together, these results show that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury, and contributes to an effective functional recovery.
Assuntos
Regeneração Nervosa , Receptores de Orexina , Traumatismos dos Nervos Periféricos , Animais , Camundongos , Compressão Nervosa , Receptores de Orexina/metabolismo , Fagocitose/genética , Nervo IsquiáticoRESUMO
Axonotmesis causes sensorimotor and neurofunctional deficits, and its regeneration can occur slowly or not occur if not treated appropriately. Low-level laser therapy (LLLT) promotes nerve regeneration with the proliferation of myelinating Schwann cells to recover the myelin sheath and the production of glycoproteins for endoneurium reconstruction. This study aimed to evaluate the effects of LLLT on sciatic nerve regeneration after compression injury by means of the sciatic functional index (SFI) and Raman spectroscopy (RS). For this, 64 Wistar rats were divided into two groups according to the length of treatment: 14 days (n = 32) and 21 days (n = 32). These two groups were subdivided into four sub-groups of eight animals each (control 1; control 2; laser 660 nm; laser 808 nm). All animals had surgical exposure to the sciatic nerve, and only control 1 did not suffer nerve damage. To cause the lesion in the sciatic nerve, compression was applied with a Kelly clamp for 6 s. The evaluation of sensory deficit was performed by the painful exteroceptive sensitivity (PES) and neuromotor tests by the SFI. Laser 660 nm and laser 808 nm sub-groups were irradiated daily (100 mW, 40 s, energy density of 133 J/cm2). The sciatic nerve segment was removed for RS analysis. The animals showed accentuated sensory and neurofunctional deficit after injury and their rehabilitation occurred more effectively in the sub-groups treated with 660 nm laser. Control 2 sub-group did not obtain functional recovery of gait. The RS identified sphingolipids (718, 1065, and 1440 cm-1) and collagen (700, 852, 1004, 1270, and 1660 cm-1) as biomolecular characteristics of sciatic nerves. Principal component analysis revealed important differences among sub-groups and a directly proportional correlation with SFI, mainly in the sub-group laser 660 nm treated for 21 days. In the axonotmesis-type lesion model presented herein, the 660 nm laser was more efficient in neurofunctional recovery, and the Raman spectra of lipid and protein properties were attributed to the basic biochemical composition of the sciatic nerve.
Assuntos
Lesões por Esmagamento , Terapia com Luz de Baixa Intensidade , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Animais , Lesões por Esmagamento/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Compressão Nervosa , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/radioterapia , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Neuropatia Ciática/patologia , Análise Espectral RamanRESUMO
The aims of the study were to determine the time-course of urinary incontinence recovery after vaginal distension (VD), elucidate the mechanisms of injury from VD leading to external urethral sphincter (EUS) dysfunction, and assess if transcutaneous electrical stimulation (TENS) of the dorsal nerve of the clitoris facilitates recovery of urinary continence after VD. Rats underwent 4-h VD, 4-h sham VD (SH-VD), VD plus 1-h DNC TENS, and VD plus 1-h sham TENS (SH-TENS). TENS or SH-TENS were applied immediately and at days 2 and 4 post-VD. Micturition behavior, urethral histochemistry and histology, EUS and nerve electrophysiology, and cystometrograms were evaluated. VD induced urine leakage and significantly disrupted EUS fibers and nerve-conduction (VD vs SH-VD group; p < 0.01). Urine leakage disappeared 13 days post-VD (p < 0.001). Structural and functional recovery of EUS neuromuscular circuitry started by day 6 post-VD, but did not fully recover by day 11 post-VD (p > 0.05). TENS significantly decreased the frequency of urine leakage post-VD (days 5-7; p < 0.01). We conclude that rat urinary continence after VD requires 2 weeks to recover, although urethra structure is not fully recovered. TENS facilitated urinary continence recovery after VD. Additional studies are necessary to assess if TENS could be used in postpartum women.
Assuntos
Parto , Estimulação Elétrica Nervosa Transcutânea/métodos , Uretra/patologia , Incontinência Urinária/terapia , Animais , Eletromiografia , Eletrofisiologia , Feminino , Compressão Nervosa , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Recuperação de Função Fisiológica , Fatores de Tempo , Incontinência Urinária por Estresse/fisiopatologia , Micção , Vagina/patologiaRESUMO
To determine whether the effects of photobiomodulation (PBM) were associated with the use of Simvastatin in the functional recovery from sciatic nerve in mice submitted to crush injury. Fifty Swiss mice (approximately 3 months old; average weight 40 g) were randomly divided into six groups: naive, sham, control, PBM (660 nm, 10 J/cm2; 30 mW; 0.6 J per day for 28 days; 0.06 cm2; 16.8 J total and 20 s), Simvastatin (20 mg/kg), and PBM/Simv (association of the two protocols). The sciatic functional index (SFI), thermal heat hyperalgesia, mechanical hyperalgesia, and thermographic evaluation were used as analyses. The evaluations were performed preoperatively and 7, 14, 21, and 28 days after the initial injury analyzed by two-way analysis of variance (ANOVA) for mixed models followed by the Bonferroni post-test. All groups except sham and naive presented an SFI compatible with severe peripheral nerve injury on the 7th day of evaluation. The PBM group presented better results in the SFI analysis (p < 0.001) on the 21st postoperative day compared to the control group. This benefit was maintained when compared to the Simvastatin (p < 0.001) and PBM/Simv groups (p < 0.01). The results of the thermal and mechanical hyperalgesia and thermography analyses were not significant (p > 0.05). The obtained results showed that PBM alone was more effective compared to Simvastatin alone or PBM combined with Simvastatin for sciatic nerve injury in mice.
Assuntos
Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Animais , Camundongos , Compressão Nervosa , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático , Neuropatia Ciática/tratamento farmacológico , Sinvastatina/uso terapêuticoRESUMO
NiResumen Objetivo: Evaluar los resultados de la retinaculotomía endoscópica para tratar el síndrome del túnel carpiano mediante la técnica de doble portal de Chow, entre enero de 2006 y diciembre de 2015. Materiales y Métodos: Estudio de 179 pacientes (edad promedio 48.2 años [rango 32-68]), con 217 casos de síndrome del túnel carpiano idiopático y un seguimiento promedio de 97.9 meses. Los pacientes eran 145 mujeres (81%) (31 bilaterales) y 34 hombres (19%) (7 bilaterales) y fueron evaluados con la Symptom Severity Scale (SSS) y la Functional Status Scale (FSS) del Boston Carpal Tunnel Questionnaire (BCTQ). Resultados: El puntaje medio de la SSS-BCTQ fue de 3,20 + 0,26 antes de la cirugía, mejoró a 1,30 + 0,12 a los 6 meses y se mantuvo en 1,25 + 0,11 a largo plazo. El puntaje medio de la FSS-BCTQ fue de 2,57 + 0,29 antes de la cirugía, mejoró a 1,28 + 0,18 a los 6 meses y se mantuvo en 1,20 + 0,09 a largo plazo. Hubo 7 casos (3,2%) de neuropraxia posquirúrgica transitoria. No hubo conversiones a técnica abierta. Conclusión: La liberación endoscópica del túnel carpiano con la técnica de Chow es un método quirúrgico eficaz y seguro para tratar el síndrome del túnel carpiano idiopático. Nivel de Evidencia; III
Objective: To evaluate the outcomes of endoscopic release of the transverse carpal ligament (TCL) in carpal tunnel syndrome (CTS) using the Chow dual-portal technique between January 2006 and December 2015. Materials and Methods: Study population consisted of 217 cases of idiopathic CTS, in 179 patients, 145 females (81%) (31 bilateral cases) and 34 males (19%) (7 bilateral cases), with an average age of 48.2 years (range, 32-68) and an average follow-up of 97.9 months. The symptom severity and functional evaluations were performed using the Boston Carpal Tunnel Questionnaire Symptoms Severity Scale (BCTQ-SSS) and the Functional Status Scale (BCTQ-FSS). Results: The average BCTQ-SSS was 3.20±0.26 in the preoperative period, which improved to 1.30±0.12 at the 6-month postoperative follow-up and remained at 1.25±0.11 in the long-term. The average BCTQ-FSS was 2.57±0.29 in the preoperative period, which improved to 1.28±0.12 at the 6-month postoperative follow-up and remained at 1.20±0.09 in the long-term. There were 7 cases (3.2%) of transient postoperative neurapraxia. No patient required to be converted to open technique. Conclusion: The endoscopic carpal tunnel release with Chow technique is an effective and safe surgical method for the treatment of idiopathic CTS. Level of Evidence; III
Assuntos
Adulto , Pessoa de Meia-Idade , Síndrome do Túnel Carpal , Nervo Mediano , Compressão NervosaRESUMO
Abstract Objective To examine the prevalence of carpal tunnel syndrome in powerlifting athletes with disabilities. Methods The present study evaluated the presence and intensity of pain (numerical scale), nocturnal paresthesia (self-report), and nerve compression (Tinel and Phalen signs) in wheelchair- and non-wheelchair-bound powerlifting athletes with disabilities. The clinical diagnosis of carpal tunnel syndrome was confirmed by the presence of two or more signs/symptoms. Results In total, 29 powerlifting athletes with disabilities were evaluated. None of the athletes reported the presence of pain or nocturnal paresthesia. The Tinel sign was present in 1 (3.45%) wheelchair-bound athlete. A positive Phalen test was present in 3 (10.35%) athletes (1 wheelchair-bound and 2 non-wheelchair-bound). Concurrent positive Tinel sign and Phalen sign tests were found in 2 (6.89%) athletes (1 wheelchair-bound and 1 non-wheelchair-bound). Conclusion Carpal tunnel syndrome was clinically diagnosed in 2 (6.89%) out of 29 powerlifting athletes with disabilities.
Resumo Objetivo Examinar a prevalência da síndrome do túnel do carpo em atletas do halterofilismo do esporte adaptado. Métodos Este estudo avaliou a presença e a intensidade da dor (escala numérica), a parestesia noturna (autorrelato), e a compressão nervosa (sinais de Tinel e de Phalen) em atletas do halterofilismo do esporte adaptado em cadeira de rodas e sem cadeira de rodas. O diagnóstico clínico da síndrome do túnel do carpo foi confirmado pela presença de dois ou mais sinais/sintomas. Resultados Vinte e nove atletas de halterofilismo de esporte adaptado foram avaliados. Nenhum dos atletas relatou a presença de dor ou parestesia noturna. O sinal de Tinel estava presente em 1 (3,45%) atleta de cadeira de rodas. O teste de Phalen positivo estava presente em 3 (10,35%) atletas (1 em cadeira de rodas e 2 sem cadeira de rodas). Testes positivos de sinais de Tinel e de Phalen foram encontrados concomitantemente em 2 (6,89%) atletas (1 em cadeira de rodas e 1 sem cadeira de rodas). Conclusão A síndrome do túnel do carpo foi diagnosticada clinicamente em 2 (6,89%) dos 29 atletas com deficiência física.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Dor , Traumatismos em Atletas , Cadeiras de Rodas , Síndrome do Túnel Carpal , Pessoas com Deficiência , Atletas , Mãos , Compressão NervosaRESUMO
Resumen La neuralgia del trigémino (NT) es una enfermedad cuya prevalencia es alta y corresponde a un porcentaje importante de neuralgias faciales; en donde las personas más afectadas son mayores de 50 años. Su manifestación clínica suele ser de cuadros de dolor facial severo y recurrentes, unilateral; en la distribución de una o más divisiones del nervio trigémino y no se explica con otro diagnóstico. El diagnóstico se basa en el cuadro clínico y usualmente no se encuentra déficit sensorial, sin embargo, si está presente se deben hacer neuroimágenes para descartar otras causas. En primera instancia está el manejo farmacológico. La carbamazepina se ha establecido como efectivo, llegando a producir un alivio del dolor dentro de las 24 horas. Cuando la farmacoterapia falla, se opta por la cirugía que se divide generalmente en dos: técnicas que destruyen la porción sensitiva del nervio; y la descompresión microvascular (DMV), que es la que tiene mejores resultados.
Abstract Trigeminal neuralgia is a disease whose prevalence is high and corresponds to a significant percentage of facial neuralgia; where the most affected people are over 50 years old. The clinical picture is usually of episodes of severe and recurring facial pain, unilateral; in the distribution of one or more divisions of the trigeminal nerve and this is not explained with another diagnosis. Diagnosis is based on the clinic and usually no sensory deficit is found, however, if present, neuroimaging should be done to rule out other causes. In the first instance is the pharmacological management. Carbamazepine has been established as effective, leading to pain relief within 24 hours. When pharmacological therapy fails, surgery is generally divided into two: techniques that destroy the sensitive portion of the nerve and microvascular decompression, which has the best results.
Assuntos
Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/tratamento farmacológico , Ponte/patologia , Microcirurgia , Compressão NervosaRESUMO
After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.