Neuroglobin protects the brain from experimental stroke in vivo

Yunjuan Sun, Kunlin Jin, Alyson Peel, Xiao Ou Mao, Lin Xie, David A. Greenberg

Research output: Contribution to journalArticle

338 Scopus citations

Abstract

Neuroglobin (Ngb) is an O2-binding protein localized to cerebral neurons of vertebrates, including humans. Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport O2, detoxify reactive oxygen species, or serve as a hypoxia sensor. We reported recently that hypoxia stimulates transcriptional activation of Ngb in cultured cortical neurons and that antisense inhibition of Ngb expression increases hypoxic neuronal injury, whereas overexpression of Ngb confers resistance to hypoxia. These findings are consistent with a role for Ngb in promoting neuronal survival after hypoxic insults in vitro. Here we report that in rats, intracerebroventricular administration of an Ngb antisense, but not sense, oligodeoxynucleotide increases infarct volume and worsens functional neurological outcome, whereas intracerebral administration of a Ngb-expressing adeno-associated virus vector reduces infarct size and improves functional outcome, after focal cerebral ischemia induced by occlusion of the middle cerebral artery. We conclude that Ngb acts as an endogenous neuroprotective factor in focal cerebral ischemia and may therefore represent a target for the development of new treatments for stroke.

Original languageEnglish
Pages (from-to)3497-3500
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
Publication statusPublished - 18 Mar 2003

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