9-(tetrahydro-2-furyl)-adenine and Infarction--Middle-Cerebral-Artery

Hepatocyte growth factor (HGF) is a multifunctional protein that exerts trophic effects on neural cells. HGF is expressed in normal brains and increased after brain injury. Recent studies suggest that neurons and astrocytes are the main producers of HGF in the brain. Here we report that microglia also produce HGF both in vitro and in vivo. Treatment of cultured microglia with prostaglandin E(2) (PGE(2)), one of the major inflammatory mediators in the brain, induced significant production of HGF, and this induction was suppressed by pretreatment with the adenylate cyclase inhibitor SQ22536, suggesting that the induction of HGF by PGE(2) in microglia proceeds via a cAMP-mediated pathway. We further investigated whether microglia also produce HGF in vivo under the pathological condition of cerebral ischemia. We found that HGF expression was increased after permanent occlusion of the middle cerebral artery (MCA), and double immunohistochemical staining revealed that the most of HGF-positive cells were microglia. PGE(2) level was increased 8 hr after start of MCA occlusion, and this enhancement is in parallel with the increase in HGF expression, suggesting that PGE(2) not only may induce HGF production in microglia in vitro but may also be an inducer in vivo.

Topics: Adenine; Adenylyl Cyclase Inhibitors; Animals; Brain Ischemia; Bucladesine; Cells, Cultured; Cyclic AMP; Dinoprostone; Enzyme Inhibitors; Hepatocyte Growth Factor; Immunohistochemistry; Infarction, Middle Cerebral Artery; Microglia; Rats