Delayed apoptotic pyramidal cell death in CA4 and CA1 hippocampal subfields after a single intraseptal injection of kainate

We have performed a detailed time-course analysis of cell death in the hipp ocampal formation, basal forebrain and amygdala following a single intrasep tal injection of kainate in adult rats. Acetylcholinesterase histochemistry revealed a profound loss of staining in the medial septum but not in the d iagonal band, and cholinergic fiber density was highly reduced in the hippo campus and amygdala at 10 days postinjection. Terminal deoxynucleotidyl tra nsferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) histochemistry was performed for precise location of apoptotic cells. Both the medial septum and amygdala exhibited numerous TUNEL-positive nuclei aft er the intraseptal injection of kainate, while the lateral septum exhibited a lower but significant incidence in terms of apoptotic cells. In the medi al septum, the presence of apoptotic cells was at a location displaying ace tylcholinesterase staining. TUNEL histochemistry revealed a time-dependent sequential apoptotic cell death in hippocampal pyramidal cells. During the first two days postinjection, apoptosis in the hippocampus was only evident in the CA3 region. At five days postinjection, the entire CA4 region becam e apoptotic. At 10 days postinjection, the whole extent of the CA1 pyramida l cell layer exhibited numerous TUNEL-positive nuclei. The time-course of k ainate-induced apoptosis in Ammons's horn correlated with the disappearance of hippocampal pyramidal neurons as detected by Nissl staining, which is s uggestive of a prominent apoptotic death for these cells. The temporal delayed distant damage to CA4 and CA1 hippocampal subfields af ter a single intraseptal kainate injection is not seen in other models empl oying kainate and may be a valuable tool for exploring the cellular mechani sms leading to cell death in conditions of status epilepticus. (C) 1999 IBR O. Published by Elsevier Science Ltd.