Impending role of hippocampal neurogenesis in the development of chronic epilepsy following seizures after Kainic acid and Pentylenetetrazol treatment

Author:

Sharma Durgesh,Jain Ayushi,Mehta Vinod Kumar,Veerwal Bharti,Shukla Sunil DuttORCID

Abstract

The study aimed to investigate how seizures contribute to abnormalities in generating new cells in the hippocampus and to explore the potential influence that these newly formed cells might have on subsequent seizure activity and the development of chronic epilepsy. The findings indicated that both pentylenetetrazol and kainic acid-induced status epilepticus resulted in neurodegeneration. There was an initial increase in cell proliferation shortly after kainic acid or pentylenetetrazol treatment. Notably, the initial seizures were associated with neurogenesis, as pentylenetetrazol-treated animals with a higher number of new neurons experienced seizures. Moreover, increased expression of neuronal nitric oxide synthase (nNOS) occurred shortly after seizures and persisted for up to 8 weeks. Elevated levels of NGF and BDNF were also observed shortly after status epilepticus or kindling. Spontaneous recurrent motor seizures seemed to be primarily caused by neuronal loss and abnormal gliosis, as they were only observed in kainic acid-treated rats with increased gliosis. Kindled rats displayed a higher rate of cell proliferation after 8 weeks of kindling, possibly due to the hyper-excited state of neurons and the establishment of a new balance between excitatory and inhibitory neurotransmitters. These results contribute to our understanding of the factors involved in the onset of seizures and the development of chronic epilepsy. Additionally, they may aid in the development of strategies for preventing and treating epilepsy. However, further investigations are necessary to explore the potential role of newly generated cells in epilepsy development.

Publisher

Qeios Ltd

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