Effect of melatonin on peripheral nerve damage resulting from tibial defect in rats / Efecto de la melatonina sobre el daño de los nervios periféricos como resultado de un defecto tibial en ratas

SUMMARY: Peripheral nerve damage (PNI) can cause demyelination, axonal degeneration and loss of motor and sensory function. Melatonin with its antioxidative effect, has been reported to reduce scar formation in nerve injury, take a role in repair process by suppressing fibroblast proliferation in the damaged area. It was aimed to investigate the effect of melatonin in the repair of peripheral nerve damage and the relationship between S100 proteins and angiogenic regulation. Wistar albino rats were divided into 3 groups. In the Defect group, 6 mm tibial bone defect using a motorized drill was created and kept immobile for 28 days. In Defect + graft group, tibial bone defect with allograft treatment was applied and kept immobile for 28 days. In Defect + graft + Melatonin group, melatonin was administered to defect + allograft group. All rats were sacrified by decapitation, skin and tibia bone were removed then fixed with 10 % neutral buffered formalin and embedded in paraffin, sections were examined under light microscopy. In the Defect+Graft group, enlargement and occlusion of the vessels with degeneration of the epineural sheath, thickening of the endoneural sheath and mild hyperplasia of schwannocytus (Schwann cells) were remarkable. In the Defect+Graft+Melatonin group, the epineural sheath was tight and regular, the axonal structures were prominent in the endoneural area. Mild S100 expression was observed in Defect+Graft group in fibers of the endoneural region with a prominent expression in schwannocytus. In Defect+Graft+Melatonin group (10mg/kg), S100 expression was moderate in areas where schwannocytus proliferated and nerve-connective tissue sheaths were reconstructed. VEGF expression was moderate in endoneural, perineural and epineural connective tissue sheaths in the Defect+Graft+Melatonin group, with negative expression in blood vessel endothelial cells, but with a positive expression in schwannocytus. We conclude that with the application of melatonin; oxidative stress decreases, schwannocytus proliferation increases, having positive influence on nerve repair with the regulation of S100 signaling and angiogenetic structuring.

RESUMEN: El daño a los nervios periféricos puede causar desmielinización, degeneración axonal y pérdida de la función motora y sensorial. Se ha informado que la melatonina, con su efecto antioxidante, reduce la formación de cicatrices en lesiones nerviosas y desempeña un papel en el proceso de reparación al suprimir la proliferación de fibroblastos en el área dañada. El objetivo de este trabajo fue investigar el efecto de la melatonina en la reparación del daño de los nervios periféricos y la relación entre las proteínas S100 y la regulación angiogénica. Ratas albinas Wistar se dividieron en 3 grupos. En el grupo Defecto, se creó un defecto óseo tibial de 6 mm con un taladro motorizado y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto, se aplicó tratamiento de defecto óseo tibial con aloinjerto y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto + Melatonina, se administró melatonina al grupo defecto + aloinjerto. Todas las ratas fueron sacrificadas por decapitación, se extrajo la piel y el hueso de la tibia y luego se fijaron con formalina tamponada neutra al 10 % y se incluyeron en parafina, las secciones se examinaron bajo microscopía óptica. En el grupo Defecto+Injerto, fueron notables el agrandamiento y la oclusión de los vasos con degeneración de la vaina epineural, engrosamiento de la vaina endoneural e hiperplasia leve de los schwannocitos (neurolemnocitos). En el grupo Defecto+Injerto+Melatonina, la vaina epineural era estrecha y regular, las estructuras axonales eran prominentes en el área endoneural. Se observó expresión leve de S100 en el grupo Defecto+Injerto en fibras de la región endoneural con una expresión prominente en los schwannocitos. En el grupo Defecto+Injerto+Melatonina, la expresión de S100 fue moderada en áreas donde proliferaron los schwannocitos y se reconstruyeron las vainas de tejido conectivo nervioso. La expresión de VEGF fue moderada en vainas de tejido conectivo endoneural, perineural y epineural en el grupo Defecto+Injerto+Melatonina, con expresión negativa en células endoteliales de vasos sanguíneos, pero con expresión positiva en schwannocitos. Concluimos que con la aplicación de melatonina; disminuye el estrés oxidativo, aumenta la proliferación de schwannocitos, influyendo positivamente en la reparación nerviosa con la regulación de la señalización S100 y la estructuración angiogenética.

Neuroprotective effects of Vitis vinifera extract on prediabetic mice induced by a high-fat diet

BACKGROUND/AIMS: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). METHODS: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). RESULTS: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls (40.95 +/- 5.40), HD (28.70 +/- 6.37), HD with 100 mg/kg (41.14 +/- 1.12), and HD with 250 mg/kg (48.98 +/- 7.01; p < 0.05, HD with VVE vs. HD). CONCLUSIONS: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.

Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

Clinical and electroneurophysiological assessment of leprosy patients on dapsone monotherapy--a two year follow-up study.

Fifty-three persons with tuberculoid type of leprosy having a thickened nerve on one side and a clinically normal nerve on the contralateral side were studied before, during and after two years of therapy for electrophysiological abnormalities in apparently normal and in obviously thickened nerves. Twenty-seven patients had received treatment with dapsone 100 mg orally and 26 cases had received rifampicin therapy. It was found that there was no extension of anesthesia or diminution of motor power over a period of two years. There was no significant difference between the initial and final recordings of motor and sensory nerve conductions if aggregate figures were taken. However, taking individual cases, deterioration in nerve conduction (increased latency and decreased velocity) was found in two patients, of whom one had received dapsone and the other had received rifampicin.

Tri-ortho-cresyl phosphate induced neurotarget esterase inhibition in brain and peripheral nerve effectively monitored by lymphocytes.

Tri-ortho-cresyl phosphate ester (TOCP: 10-100 mg/kg)--an organophosphorus compound (OP) inhibited brain, peripheral nerve and lymphocyte neurotarget esterase activities in a dose related and time-dependent manner. There was a good correlation of inhibition between brain, peripheral nerve and lymphocyte tissues taken from adult hens treated with 3 different doses of TOCP and sacrificed 24 and 48 hr after exposure. The results suggest that lymphocyte can effectively monitor OP compounds for investigating inhibition of neurotarget esterase activity in brain and peripheral nerve tissues.

Effect of drug treatment on electroneurological measures of peripheral nerve function in leprosy patients.

OBJECTIVE: To investigate whether drug treatment improves the electroneurological measures of affected peripheral nerve function in leprosy patients. DESIGN: Clinical status of patients determined on the first visit by an investigator administered, pre-designed questionnaire, followed by measurement of motor conduction velocity (MCV) and distal latency (DL) of ulnar, median, common peroneal and posterior tibial nerves bilaterally in patients referred consecutively from the dermatology unit and leprosy clinic, Teaching Hospital, Galle. MCV and DL measurements were repeated after 6 to 12 months of treatment. SETTING: Department of Physiology, Faculty of Medicine, University of Ruhuna, Galle. SUBJECTS: 24 diagnosed leprosy patients; tuberculoid, lepromatous and borderline in clinical type. INTERVENTIONS: Based on clinical typing. Tuberculoid (paucibacillary) type rifampicin 600 mg monthly and dapsone 100 mg daily for six months. Lepromatous and borderline (multibacillary) type rifampicin 600 mg and clofazimine 300 mg monthly and dapsone 100 mg and clofazimine 50 mg daily for 24 months. RESULTS: DL in all 4 nerves and MCV in 3 nerves tested were significantly different (p > 0.001) to those for the normal population and remained so after 6 to 12 months of treatment. The DL in the ulnar nerve showed significant improvement (p < 0.05) after treatment. When analysed in each patient individually, before and after treatment, the MCV showed an improvement in 48 to 72% of patients and the DL in 41 to 59%, but differences were not significant. CONCLUSIONS: Electroneurological recovery (return to normal state) of the affected peripheral nerves of leprosy patients does not occur after 6 to 12 months of drug treatment. The significant (p < 0.05) improvement (becoming better) of ulnar nerve DL indicates that, if at all, electroneurologically detectable improvement of nerve function occurs in the early stages of nerve damage, and that it may take longer than one year after starting treatment.

Polineuropatia periférica induzida por Benzonidazol no tratamento da doença de Chagas / Peripheral polyneuropathy induced by benzonidazole in the treatment of Chagas' disease

O estudo evolutivo de pacientes na fase crônica da doença de Chagas, feito antes e após o tratamento experimental com benzonidazol, evidenciou ser esta droga tóxica para o sistema nervoso periférico, dose dependente, com possível efeito cumulativo em vários pacientes. A polineuropatia foi predominantemente do tipo axonal e mais severa nos pacientes já com evidências neurofisiológicas de desnervaçäo periférica antes do tratamento

Neurotoxicidad periférica en paciente tratadas con cisplatino (DDP) y adriamicina (ADR) / Peripheral neurotoxicity in patients treated with cisplatin (DDP) and adriamycin (ADR)

La neurotoxicidad ha sido descripta como una complicación de poca jerarquía en los pacientes tratados con DDP y no está descripta en el hombre para la ADR. Sin embargo con la combinación de ambas drogas en un grupo de 12 pacientes se encontró el 42 por ciento (42 pc.) de complicaciones neurológicas importantes al llegar a la dosis acumulativa de 350 mg/m2 de DDP y 120 mg/m2 de ADR