1Neurology Department, Zhongshan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,
Fudan University, Shanghai 200032, China
2Department of Anaesthesia, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200032, China

Abstract 

Pentylenetetrazole (PTZ) is a widely-used convulsant used in studies of epilepsy; its subcutaneous injection generates an animal model with stable seizures. Here, we compared the ability of PTZ via the intravenous and subcutaneous routes to evoke progressive epileptiform activity in the hippocampal CA1 neurons of anesthetized rats. The involvement of the BDNF-TrkB pathway was then investigated. When PTZ was given intravenously, it induced epileptiform bursting activity at a short latency in a dose-dependent manner. However, when PTZ was given subcutaneously, it induced a slowly-developing pattern of epileptogenesis; first, generating multiple population-spike peaks, then spontaneous interictal discharge-like spike, leading to the final ictal discharge-like, highly synchronized bursting fi ring in the CA1 pyramidal layer of the hippocampus. K252a, a TrkB receptor antagonist, when given by intracerebroventricular injection, signifi cantly reduced the probability of multiple population spike peaks induced by subcutaneous injection of PTZ, delayed the latency of spontaneous spikes, and reduced the burst frequency. Our results indicate that PTZ induces a progressive change of neuronal epileptiform activity in the hippocampus, and the BDNF-TrkB signaling pathway is mainly involved in the early phases of epileptogenesis, but not the synchronized neuronal burst activity associated with epileptic seizure in the PTZ animal model. These results provide basic insights into the changing pattern of hippocampal neuronal activity during the development of the PTZ seizure model, and establish an in vivo seizure model useful for future electrophysiological studies of epilepsy.

Keywords

epilepsy; pentamethylenetetrazole; hippocampus; BDNF; TrkB

[SpringerLink]