PT - JOURNAL ARTICLE AU - Kunlin Jin AU - Xiao Ou Mao AU - Yunjuan Sun AU - Lin Xie AU - Lan Jin AU - Eiichiro Nishi AU - Michael Klagsbrun AU - David A. Greenberg TI - Heparin-Binding Epidermal Growth Factor-Like Growth Factor: Hypoxia-Inducible Expression <em>In Vitro</em> and Stimulation of Neurogenesis <em>In Vitro</em> and <em>In Vivo</em> AID - 10.1523/JNEUROSCI.22-13-05365.2002 DP - 2002 Jul 01 TA - The Journal of Neuroscience PG - 5365--5373 VI - 22 IP - 13 4099 - http://www.jneurosci.org/content/22/13/5365.short 4100 - http://www.jneurosci.org/content/22/13/5365.full SO - J. Neurosci.2002 Jul 01; 22 AB - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is found in cerebral neurons, and its expression is increased after hypoxic or ischemic injury, which also stimulates neurogenesis. To investigate the possible role of HB-EGF in hypoxic–ischemic induction of neurogenesis, we measured its expression, effects, and target receptors in embryonic murine cerebral cortical cultures and in adult rat brain. Hypoxia increased HB-EGF expression by ∼50% in cortical cultures, where expression was associated with mature and immature neurons. HB-EGF (5–100 ng/ml) stimulated by ∼80% the incorporation of bromodeoxyuridine (BrdU) into cultured cells that expressed the HB-EGF receptors epidermal growth factor receptor (EGFR)/avian erythroblastic leukemia viral oncogene homolog 1 (ErbB1) and N-arginine dibasic convertase (NRDc). Intracerebroventricular administration of HB-EGF in adult rats increased BrdU labeling in the subventricular zone and in the subgranular zone of dentate gyrus, where EGFR/ErbB1 and NRDc were also expressed and where ischemia-induced neurogenesis is observed. We conclude that HB-EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR/ErbB1 and possibly NRDc. Therefore, HB-EGF may help to trigger proliferation of neuronal precursors in brain after hypoxic or ischemic injury.