Neuroglobin protects the brain from experimental stroke in vivo.
Neuroglobin (Ngb) is an O(2)-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 O(2), 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.
Sun
Yunjuan
Y
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Jin
Kunlin
K
Peel
Alyson
A
Mao
Xiao Ou
XO
Xie
Lin
L
Greenberg
David A
DA
D000595:Amino Acid Sequence; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D000229:Dependovirus / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors; D005914:Globins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000078787:Neuroglobin; D018696:Neuroprotective Agents / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D020319:Oligodeoxyribonucleotides, Antisense; D005914:Globins