Abstract 2053 Neurology Platform, Sunday, 5/2

Activation of c-Jun N-terminal kinase (JNK) and prolonged increase in c-Jun expression and phosphorylation observed in adult rat models of transient middle cerebral artery (MCA) occlusion is thought to contribute to apoptotic cell death following reperfusion. Survival after injury to the adult brain, however, is also associated with increased c-Jun expression. In the normal developing nervous system, the basal level of c-Jun expression is much higher compared to that in the juvenile and adult CNS. Our aim was to establish the role of JNK pathway in the neonatal ischemia-reperfusion-induced brain injury. P7 rats were subjected to transient intraluminal MCA occlusion (Derugin, et.al., Neurosci. Res., 1998). Three hours later, reperfusion was achieved by removal of the suture. TTC and Nissl staining were performed 24 hours later (n=11). The presence of total and phosphorylated JNK (p-JNK) and cJun were assayed by Western blot analysis in the cortex, caudate nuclei and hippocampus of control rats and rats at 3 and 24 hours after reperfusion (n=3-4 per group). JNK kinase assay was performed using the same tissue samples. c-Jun expression was determined using immunohistochemistry (n=4). Infarcts were seen in 80% of rats and included 38.7±13.6% (mean±SD) of the ischemic hemisphere. No significant changes in c-Jun, JNK1 and JNK2 expression ipsilateral to MCA occlusion were observed in three anatomical regions studied using Western blot. A transient increase in c-Jun phosphorylation ipsilateral to the occlusion was observed at three hours after reperfusion. Density of strongly c-Jun immunoreactive cells appeared to be higher ipsilateral in regions of infarction. The unilateral nature and regional specificity of this response suggests involvement of JNK pathway in ischemia-induced brain injury in the neonatal brain.

Supported by NIH grant P50 NS 35902 and REAC grant, UCSF