Susceptibility to pentylenetetrazol-induced and audiogenic seizures in rats given aspirative lesions of the fimbria-fornix pathways followed by intrahippocampal grafts: a time-course approach

Abstract

Long-Evans female rats sustained aspirative lesions of the fimbria-fornix pathways and part of the overlying structures (Lesion). Eight or 9 days later, one third of these lesioned rats received intrahippocampal septal cell suspension grafts (Sept-G) and another third received grafts of hippocampal origin (Hipp-G). Sham-operated rats (Sham) served as controls. For each surgical treatment, 3 subgroups were assigned to one of 3 experiments which differed by the delay separating grafting from testing. Three months (EXP1), seven months (EXP2) and twelve months (EXP3) after grafting, rats were tested for reactivity to pentylenetetrazol (PTZ, 30 mg/kg, i.p.) and to sound (10–20 kHz peaks, 120 dB, 90 s), two models of generalized convulsive seizures. Three months after grafting, lesion-only rats showed increased reactivity to PTZ as compared to Sham rats; both types of grafts (Sept-G, Hipp-G) attenuated this lesion-induced effect. Whether 7 or 12 months after grafting, no significant between-group differences were observed anymore. Three months after grafting, reactivity to sound tended to increase in lesion-only rats and was significantly increased in both groups with grafts (Sept-G, Hipp-G) as compared to the Sham group. Seven months after grafting, only Hipp-G rats showed increased reactivity to sound compared to Sham or lesion-only rats. No significant between-group difference was observed at 12 months post-grafting. At all 3 delays, histological analyses revealed well integrated grafts, but only septal grafts provided the denervated hippocampus with an AChE-positive fiber ingrowth. Reactivity to PTZ or to sound was correlated neither with the size of the graft, nor with the acetylcholinesterase (AChE)-positive graft-derived reinnervation of the dorsal hippocampus. The present results suggest that hippocampal denervation may result in a temporary increase in reactivity to PTZ and susceptibility to sound, the former being transitorily attenuated and the latter being transitorily increased by both kinds of grafts. Our data confirm earlier reports showing that grafts may influence sensitivity to convulsive seizure-inducing treatments. In addition, these data indicate that this influence is not necessarily lasting and that the kind and duration of this influence is dependent upon the model of convulsive seizures used.