Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with G ABA in double-labeling studies performed in the hippocampal formation (exce ption made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neuro l 1993:331:111-121). In this sense, it further characterizes an extremely i mportant cell category due to the relevant involvement of inhibitory system s in the mechanisms of genesis and propagation of seizures. Here, we assess ed the histochemistry for NADPHd in the hippocampal complex: of chronic pil ocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of t he polymorphic layer of the dentate gyrus (hilus) presented one of the high est losses of NADPHd-positive cells (55-79%) in the hippocampus. A signific ant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, an d radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular py ramidal cell layer was not different from that observed in controls. A sign ificant loss of NADPHd-stained cells was observed in entorhinal cortex laye rs II and III in the epileptic group. For entorhinal cortex layers V and VI , however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocam pal formation. There has been a growing support for the notion that GABAerg ic neurons in the hippocampal formation are not equally sensitive to insult s. Our results suggest that, as a marker for a subpopulation of GABAergic n eurons, NADPHd helps in further refining the characterization of the differ ent neuronal populations sensitive to epileptic activity. (C) 1999 Wiley-Li ss, Inc.