REVERSIBLE ISCHEMIA INCREASES LEVELS OF ALZHEIMER AMYLOID PROTEIN-PRECURSOR WITHOUT INCREASING LEVELS OF MESSENGER-RNA IN THE RABBIT SPINAL-CORD

In a rabbit spinal cord ischemia model (RSCIM), the time courses of ne uropathological damage of the spinal cord and neurological impairment of the motor functions are well established, demonstrating that the ex tent of neuropathological damage and the severity of neurological impa irment are closely correlated. We used the RSCIM to elucidate the effe cts of reversible (15 min) and irreversible (60 min) ischemia on the e ndogenous levels of amyloid protein precursors (APPs) at both the mRNA and protein levels in the caudolumbar/sacral region of the spinal cor d. We speculate that endogenous APPs are induced by ischemia as either trophic factors or stress-induced proteins in the RSCIM. A 15-min occ lusion transiently increased the APP protein levels in neurons, which returned to the original levels by the end of 60 min occlusion. The in crease in APP protein levels during 15-min ischemic insult does not ap pear to involve regulation at the mRNA level. The increased level of A PPs, particularly of the soluble form, could support the possibility t hat APPs play a neuroprotective role in the RSCIM as stress-induced pr oteins. In contrast, failure to maintain the increased APP protein lev els or to increase the mRNA, as seen in the 60-min ischemia samples, m ay be one of the causal factors that induce necrosis and neuronal cell death leading to irreversible neurological impairment.