INDUCTIONS OF HEPATOCYTE GROWTH-FACTOR AND ITS ACTIVATOR IN RAT-BRAINWITH PERMANENT MIDDLE CEREBRAL-ARTERY OCCLUSION

Hepatocyte growth factor (HGF) is a potent pleiotrophic peptide which has a trophic role for neuronal cells. As it exerts its effect only af ter a conversion to its heterodimeric active form, the activation step , which is catalyzed by an enzyme serine protease named HGF activator (HGFA), is of great importance. HGF activated by HGFA may act as a pro tecting agent in injured brain. In the present study, we investigated expression of immunoreactive HGF and HGFA in rat brain after permanent middle cerebral artery (MCA) occlusion. By immunohistochemical analys is, HGF and HGFA were normally expressed only in ependymal cells and c horoid plexus. At 1 h after MCA occlusion, neurons in the ischemic pen umbra region of the cerebral cortex slightly expressed immunoreactive HGFA. HGF was not induced at that time. At 3 h of ischemia, however, i mmunoreactive HGF as well as HGFA became detectable in neurons of the ischemic cerebral cortex and caudate. Immunoreactivity for HGF continu ed to increase until 24 h, while that for HGFA remained almost constan t from 3 to 24 h. No glial or vascular endothelial cells expressed HGF nor HGFA. By Western blot analysis for HGF, a single band of molecula r weight (MW) 34 kDa became apparent at 24 h, corresponding to the Lig ht chain of the active form HGF. The present study suggests that HGF a nd HGFA were induced in neurons under permanent ischemia with slightly different temporal profiles. Through activation by HGFA, the active f orm of HGF could serve as a neurotrophic factor in ischemic brain. (C) 1998 Elsevier Science B.V. All rights reserved.