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Published on: November 8, 2018
Neuroprotective effects of Vitamin D3 supplementation combination with valproate and perampanel in an experimental
Sudhir Chandra Sarangi1, Surabhi Sinha1, Shan Mohamad1
1Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Background:
Status epilepticus (SE) is a severe form of epilepsy with neurological sequelae and high mortality. Considering the neuromodulatory effects of Vitamin D3 (Vit-D3), this study investigated the potential role of Vit-D3 alone and in combination with antiseizure medications (ASMs).
Materials And Methods:
Male Wistar rats were assigned into seven groups: SE-control, healthy control, valproate (VPA) (370 mg/kg), perampanel (PER) (1.5 mg/kg), Vit-D3 (6000 IU/kg/day), VPA + Vit-D3, and PER + Vit-D3. After 14 days of pretreatment, SE was induced by LiCl-pilocarpine administration, followed by acute (17 days) and long-term (29 days) drug effect studies. Seizure details and learning-memory were assessed along with evaluation of brain tissue for neurodegeneration (electronmicroscopy), histopathology, neuronal viability (neuron-specific nuclear protein), reactive astrocytes (glial fibrillary acidic protein) by immunohistochemistry, total antioxidant capacity, and neuroinflammation biomarkers.
Results:
Vit-D3 combination with VPA or PER significantly reduced the percentage of rats experiencing stage-3/4 seizures and increased latency compared to the SE-control group (P < 0.001). Drug-treated groups had better memory retention (P < 0.001) than SE-control, with significantly better protection in the combination group. In immunohistochemistry, Vit-D3 in combination with ASMs had less neurodegeneration and reactive astrocytes in the hippocampus and cerebral cortex (P < 0.001). Through electron microscopy, the SE-control group exhibited significant damage in hippocampus's myelin sheath and axons (grade 3) on days 17 and 29. Vit-D3 alone and in combination with ASMs attenuated these changes (P < 0.001), with combination groups showing the least neurodegeneration (day 29).
Conclusion:
Vit-D3 supplementation, especially in combination with ASMs, showed promising neuroprotective effects in the SE model in rats by improving seizure control, memory, hippocampal health, and antioxidant levels.
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