POSTISCHEMIC TREATMENT WITH A LAZAROID (U74389G) PREVENTS TRANSIENT GLOBAL ISCHEMIC DAMAGE IN RAT HIPPOCAMPUS

The ability of an experimental lazaroid, U74389G, to prevent damage to hippocampal CA1 cytoarchitecture due to transient global ischemia was studied by light and electron microscopy. Postischemic rats were give n a single i.p. dose of lazaroid (6 or 18 mg kg(-1)) at 5 min after re vival by cardiopulmonary resuscitation (CPR). Without lazaroid treatme nt the number of normal-appearing neurons in the CA1 region declined f rom a normal value of 15.49+/-2.21 to 8.40+/-10.08 per 100 mu m(2) on day 7 after the ischemic episode, and there was extensive damage visib le in the cytoarchitecture of this region. In lazaroid treated rats, t he normal cytoarchitecture was retained and the number of normal-appea ring cells was maintained at 15.10+/-2.22 per 100 mu m(2). Ultrastruct ure studies indicated that pyknotic pyramidal cells laden with lysosom al aggregates were common in untreated post-ischemic rats but rare in lazaroid-treated rats. These results indicate that U74389G maintained the structural integrity of this region of the brain after transient g lobal ischemia and suggest that this lazaroid may be an effective neur oprotectant.