EXPRESSION OF NERVE GROWTH-FACTOR AND TRKA AFTER TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN RATS

Background and Purpose-In vitro studies have shown that nerve growth f actor (NGF) is protective to cortical neurons against various insults. However, the role of NGF in relation to its high-affinity trkA recept or in the cortical neurons has not been well discussed. In this experi ment, we studied the possible involvement of the NGF/receptor system i n the ischemic injury of cortical neurons after focal cerebral ischemi a in rats. Methods-Male Wistar rats received right middle cerebral art ery occlusion of 90 minutes' duration. The rats were decapitated at di fferent reperfusion time points: hour 4 and days 1, 3, 7, and 14 of re circulation. Brain sections at the level of striatum were immunostaine d against NGF, trkA, glial fibrillary acidic protein (GFAP), and stres s protein HSP70, Double immunostaining against NGF and GFAP was also p erformed. Optical density of NGF immunoreactivity in the ischemic and nonischemic cortexes was compared between sham-control and ischemic an imals. Results-In the sham-control rats, NGF immunoreactivity was pres ent in the cortical and striatal neurons. However, beginning at hour 4 after recirculation, there was a significant decrease of NGF in the i schemic cortex and striatum, Beginning at day 1, NGF was absent comple tely in the infarcted striatum and cortex. However, in the peri-infarc t penumbra area, despite a decrease in NGF at hour 3 and day 1, NGF re covered beginning at day 3 and returned almost to the sham-control lev el at day 14. In the nonischemic cortex, NGF increased beginning at ho ur 4, peaked at day 7, and returned almost to the sham-control level a t day 14, The trkA and HSP70 immunoreactivities were not present in th e sham-control cortex. However, trkA was induced at hour 4 in the isch emic cortex and at days 1 and 3 in the peri-infarct penumbra cortex, T he HSP70 was induced at days 1 and 3 in the peri-infarct penumbra area . Double immunostaining showed that the number of GFAP-positive cells increased gradually, and NGF immunoreactivity in the GFAP-positive cel ls became gradually intense after ischemia. Conclusions-Our study demo nstrated a temporal profile of NGF and trkA in the ischemic cortex and NGF expression by reactive astrocytes. Our data suggest that the NGF/ receptor system may play a role in the astrocyte/neuron interaction un der certain pathological conditions, such as focal cerebral ischemia.