THE SUSCEPTIBILITY OF CA1 PYRAMIDAL CELLS TO CEREBRAL-ISCHEMIA IS MAINTAINED AFTER NEONATAL, LESION-INDUCED REORGANIZATION OF THE HIPPOCAMPAL CIRCUITRY

Acute lesions of hippocampal pathways have been shown previously to am eliorate CA1 pyramidal cell loss after subsequent transient cerebral i schemia. In this study, we examined the effect of chronic neonatal les ion with reorganization of hippocampal circuitry on adult postischemic neuron loss in the hippocampus. Newborn rats were subjected to unilat eral knife-cut lesions at various positions along the trisynaptic ento rhino-dentato-hippocampal pathway. Seven months later, the rats were s ubjected to transient cerebral ischemia using the four-vessel occlusio n technique. At the time of killing 4 days later, a Nissl stain was us ed to demonstrate neuronal degeneration, while connective reorganizati on resulting from the neonatal lesions was monitored by Timm staining. In one group of rats, neonatal lesions had caused severe depletion of entorhinal projections to the septodorsal fascia dentata and hippocam pus (CA1 and CA3), without any direct damage to the dorsal hippocampus itself. Another group had extensive damage of the dorsal CA3, with re moval of the Schaffer collaterals from these levels to CA1, and variab le damage to the entorhinal afferents. In both groups, the extent and pattern of ischemia-induced degeneration of CA1 pyramidal cells were t he same on the lesioned and nonlesioned sides of the brain, demonstrat ing that neonatal lesions and the subsequent connective reorganization did not have a sparing effect. Seen in relationship to previous obser vations in adult rats of the neuroprotective actions of acute, preisch emic lesions of the trisynaptic hippocampal pathway, it is concluded t hat CA1 pyramidal cell loss requires the presence of intact excitatory afferents rather than an intact hippocampal circuitry.