GABAergic neurons are spared after intrahippocampal kainate in the rat

The present study used Nissl stains and glutamate decarboxylase immunoreactivity (GAD-IR) to quantify the acute and chronic toxicity of kainic acid (KA) on focal and remote hippocampal principal neurons (i.e., pyramidal and granule cells) and on putative inhibitory neurons (GAD-IR or GABAergic) following intrahippocampal KA administration. Concentrations of 0.5, 1.0, 1.25 or 1.5 micrograms KA/0.2 microliters were injected unilaterally into the posterior hippocampus of rats (n = 32), with survival periods of 1, 3, 5, 14, 21, 30 and 60 days. The age-matched control animals (n = 10) received an intrahippocampal injection of 0.2 microliter saline (sham control, n = 4) or no injection (normal, n = 6). The ipsilateral (KA+) cell counts demonstrated a selective vulnerability of CA3 and CA4 pyramidal neurons which was maximal at 14 days and unchanged to 60 days. However, in the same region, putative inhibitory (GAD-IR) neurons were resistant to the neurotoxic effects of KA. Contralateral (KA-) pyramidal cell and GAD-IR neuron densities were equivalent to controls. The present data demonstrate a selective resistance to KA by GABA neurons compared to the vulnerability of pyramidal neurons. Because GABA neurons are relatively spared in the KA focus, loss of GABAergic inhibitory neurons is probably not a mechanism for the seizure sensitivity in the KA model.