1. ^*Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
2. ^†Department of Biochemistry, Osaka University Medical School, Osaka, Japan
3. ^‡Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
4. ^§CREST (Core Research for Evolutional Science and Technology), Japan Science and Technology Cooperation, Saitama, Japan

Correspondence: Nobutaka Kawahara, Department of Neurosurgery, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113, Japan.

Received 2 February 1998; Revised 4 June 1998; Accepted 4 June 1998.

Abstract

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor- (TGF-) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the like-lihood that HB-EGF is a neuroprotective factor in cerebral ischemia.