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This work tested the role of carbamazepine in alleviating alloxan-induced diabetic neuropathy and the enhancement of spinal plasticity. Mice were randomized into four groups: normal, control, carbamazepine (25-mg/kg) and carbamazepine (50-mg/kg). Nine weeks after induction of diabetes, symptoms of neuropathy were confirmed and carbamazepine (or vehicle) was given every other day for five weeks. After completing the treatment period, mice were sacrificed and the pathologic features in the spinal cord and the sciatic nerves were determined. The spinal cords were evaluated for synaptic plasticity (growth associated protein-43, GAP43), microglia cell expression (by CD11b) and astrocyte expression (glial fibrillary acidic protein, GFAP). Further, sciatic nerve expression of Nav1.5 was measured. Results revealed that carbamazepine 50 mg/kg prolonged the withdrawal threshold of von-Frey filaments and increased the hot plate jumping time. Carbamazepine improved the histopathologic pictures of the sciatic nerves and spinal cords. Spinal cord of carbamazepine-treated groups had enhanced expression of GAP43 but lower content of CD11b and GFAP. Furthermore, specimens from the sciatic nerve indicated low expression of Nav1.5. In conclusion, this work provided evidence, for the first time, that the preventive effect of carbamazepine against diabetic neuropathy involves correction of spinal neuronal plasticity and glia cell expression.

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy. [ABSTRACT FROM AUTHOR]