Modulation of Cypermethrin and PTZ-induced Astrogliosis and GABAergic Interneuron Loss in the Septal Nucleus by Vitamin E and Valproic Acid Co-Therapy

Exposure to environmental neurotoxicants is linked to neurological effects of epilepsy, impacting not only seizure severity but also neuroglial integrity across different brain regions. This study investigated the effects of Vitamin E and Valproic Acid on neuronal and glial changes in the septal nucleus of rats exposed to pentylenetetrazol-induced seizures and cypermethrin. Fifty-six male Wistar rats were divided into control and experimental groups in a two-phase design, receiving various combinations of pentylenetetrazol, cypermethrin, Vitamin E, and valproic acid. Septal sections underwent Hematoxylin and Eosin staining, along with immunohistochemical markers for astrogliosis (GFAP) and Gamma-Aminobutyric Acidergic interneurons (Parvalbumin). Cypermethrin or Pentylenetetrazol significantly decreased parvalbumin-positive interneurons and GFAP+ astrocyte expression in the septal nucleus, with observable degenerative features in the septal neuronal cytoarchitecture. Conversely, VPA and Vitamin E, whether alone or combined, partially restored PV-positive interneurons and GFAP+ astrocytic expressions, indicating partial preservation of astrocytes, with the combination showing the greatest improvement. There was also a cumulative structural recovery in the overall cytoarchitecture with combined treatment. These findings suggest that cypermethrin contributes to septal neuropathology in seizure models, and that combined antioxidant and antiepileptic therapy may partly reduce astrocytic and neuronal loss.

Key Words: cypermethrin, epilepsy, astrogliosis, GABAergic interneuron, septal nuclei