Inducible nitric oxide synthase appears and is co-expressed with the neuronal isoform in interneurons of the rat hippocampus after transient ischemia induced by middle cerebral artery occlusion.

The hippocampus (dentate gyrus DG plus Cornu Ammonis, CA) is vulnerable to neuropathological events such as ischemia. The DG is a region where neurogenesis takes place and it has been demonstrated that ischemia stimulates neurogenesis. Nitric oxide (NO) plays a major role in ischemic damage evolution and increases in rat hippocampus after ischemia. No information is available on the presence of nNOS-immunoreactive (IR) neurons in the hippocampus of ischemic animals; whereas, the presence of the iNOS protein has been reported in the DG after focal ischemia. We evaluated, immunohistochemically, the cell types expressing nNOS and iNOS in the rat hippocampus by 24 up to 144 h after transient middle cerebral artery occlusion to ascertain whether ischemia induces changes in nNOS or iNOS expression and whether a relationship exists between these changes and the animal survival. nNOS-IR interneurons were detected in control and ischemic rats; in the latter, their number was significantly decreased at all time points. iNOS-IR interneurons appeared in the hippocampus of ischemic rats at 24 h; their number was significantly higher in the animals with longer survival and did not change at later time points. More than 50% of the nNOS-IR interneurons co-expressed iNOS-IR. All these changes were seen both in the ipsilateral and contralateral hippocampus. In conclusion, the focal ischemia affects the hippocampus which responds bilaterally to the injury. We hypothesize that the decrease in the nNOS-IR neurons is likely due to either a neuronal loss or a switching towards the iNOS production which, by inducing neurogenesis, might compensate the neuronal loss.