Mechanical Allodynia and Thermal Hyperalgesia in Diabetic Mice and Neurodegenerative Changes in the Spinal Cord and Sciatic Nerves: Modulation by Topiramate | ||||
| The Medical Journal of Cairo University | ||||
| Volume 91, Issue 12, December 2023, Page 1585-1599 PDF (1.32 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/mjcu.2024.342763 | ||||
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| Author | ||||
| FATEN ABBAS , MD.*; HOWAIDA S. ALI, M.D.** DALIA IBRAHIM, M.D.* | ||||
| The Department Physiology*, Faculty of Medicine, Suez Canal University and Pharmacology Department**, Faculty of Medicine, Assiut University | ||||
| Abstract | ||||
| Abstract Background: Diabetes-related pathological alterations in body organs may take place due to immunological reactions and inflammatory/oxidative burden. Aim of Study: The current study aimed to test the neuropro-tective effect of topiramate in an animal model of peripheral di-abetic neuropathy (DN) and test its ability to suppress the spinal cord inflammatory burden and glial reactivity. Material and Methods: The study was carried out in Fac-ulty of Medicine, Suez Canal University, Male adult mice were assigned as vehicle group, DN group (alloxan 180mg/kg, i.p.), DN+topiramate 10-mg/kg and DN+topiramate 30-mg/kg. Mice received topiramate therapy for four weeks then tested for allo-dynia and hyperalgesia. Spinal cord specimens were examined by molecular assays, light microscopic technique and neurofila-ment heavy chain (NEFH) immunostaining Sciatic nerves were examined microscopically. Results: Indicated that DN mice had lower the hotplate la-tency time (0.46-fold of latency to licking) and lower the von-Frey test pain threshold (0.6-fold of filament size). In contrast, treatment with topiramate increased these values. Sciatic nerve showed axonal degeneration, demyelination, loss of some cen-tral axons, and shrunken Schwann cells. Further, spinal cords of DN mice had elevated levels of GFAP (5.6-fold) and lower GAP-43 (0.25-fold), inflammatory cytokines (-3 or 4-fold) and neuronal degeneration with dystrophic neurons. Conclusion: Topiramate produced neuroprotection and increased pain thresholds in mice with DN, suppressed spinal cord inflammation and GFAP but enhanced plasticity as indi-cated by higher GAP-43 protein level. Hence, our study rein-forces topiramate as neuroprotection and suggests it for allevi-ating neuropathic pain. | ||||
| Keywords | ||||
| GFAP — Mouse diabetic neuropathy — Neurofila; ment — Pain test — Sciatic nerve — Spinal cord | ||||
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