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(Stroke. 1998;29:1687-1697.)
© 1998 American Heart Association, Inc.

Original Contributions

Expression of Nerve Growth Factor and trkA After Transient Focal Cerebral Ischemia in Rats

Tsong-Hai Lee, MD, PhD; Hiroyuki Kato, MD, PhD; Sien-Tsong Chen, MD; Kyuya Kogure, MD, PhD; Yasuto Itoyama, MD, PhD

From the Second Department of Neurology, Chang Gung Memorial Hospital, Taipei, Taiwan (T.-H.L., S.-T.C.); the Department of Neurology, Tohoku University School of Medicine, Sendai, Japan (H.K., Y.I.); and the Foundation for Brain and Nerve Diseases and the Institute of Neuropathology, Kumagaya, Japan (K.K.).

Background and Purpose—In vitro studies have shown that nerve growth factor (NGF) is protective to cortical neurons against various insults. However, the role of NGF in relation to its high-affinity trkA receptor in the cortical neurons has not been well discussed. In this experiment, we studied the possible involvement of the NGF/receptor system in the ischemic injury of cortical neurons after focal cerebral ischemia in rats.

Methods—Male Wistar rats received right middle cerebral artery occlusion of 90 minutes' duration. The rats were decapitated at different reperfusion time points: hour 4 and days 1, 3, 7, and 14 of recirculation. Brain sections at the level of striatum were immunostained against NGF, trkA, glial fibrillary acidic protein (GFAP), and stress protein HSP70. Double immunostaining against NGF and GFAP was also performed. Optical density of NGF immunoreactivity in the ischemic and nonischemic cortexes was compared between sham-control and ischemic animals.

Results—In the sham-control rats, NGF immunoreactivity was present in the cortical and striatal neurons. However, beginning at hour 4 after recirculation, there was a significant decrease of NGF in the ischemic cortex and striatum. Beginning at day 1, NGF was absent completely in the infarcted striatum and cortex. However, in the peri-infarct penumbra area, despite a decrease in NGF at hour 4 and day 1, NGF recovered beginning at day 3 and returned almost to the sham-control level at day 14. In the nonischemic cortex, NGF increased beginning at hour 4, peaked at day 7, and returned almost to the sham-control level at day 14. The trkA and HSP70 immunoreactivities were not present in the sham-control cortex. However, trkA was induced at hour 4 in the ischemic cortex and at days 1 and 3 in the peri-infarct penumbra cortex. The 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 cells became gradually intense after ischemia.

Conclusions—Our study demonstrated 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 under certain pathological conditions, such as focal cerebral ischemia.

Editorial Comment

Christopher D. Kontos, MD, Guest Editor

Division of Cardiology, Duke University Medical Center, Durham, North Carolina

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