Neuroprotective Effect of Nilotinib on Cortical Pyramidal Cells, Histological, Morphometric and Biochemical Study

Abstract

Introduction: Death of neuronal cell and gliosis are the two main pathological hallmarks induced by nervous tissue stress like conditions such as status epilepticus. Previous studies have mentioned that neuronal cell death occur as a result of different mechanisms, namely, necrosis and apoptosis. Although more recent studies have explained the cell death on the basis of autophagy. Many antiepileptic drugs are marketed, taking into consideration the antioxidant role of nilotinib and support its use as a favorable antiepileptic drug. The aim of the present study is to assess the neuroprotective effect of antiepileptic drug nilotinib on cortical tissue in rats. Materials and Methods: Sixty adult male rats were divided into three groups: (1) Control group, (2) pentylenetetrazol group (injected with pentylenetetrazol 60 mg/kg, subcutaneously), (3) nilotinib and pentylenetetrazol group (pretreated with nilotinib, 25 mg/kg daily for seven days prior to pentylenetetrazol administration). Latency of seizure and level of either oxidant or antioxidant enzymes in the cortical tissue was assessed. The histopathological changes in the cerebral cortex were studied also using hematoxylin and eosin stain. Results: Nilotinib increased the latency period of convulsions, increased the antioxidant enzymes levels with regain of the normal histological features. Conclusions: Nilotinib proved to promote the antioxidant, antiapoptotic pathways, anti-inflammatory and inhibiting autophagy which favor its use as an anti-epileptic drug.