Mechanisms of hyperbaric oxygen-induced neuroprotection in a rat model of subarachnoid hemorrhage.
Acute cerebral ischemia occurs after subarachnoid hemorrhage (SAH) because of increased intracranial pressure (ICP) and decreased cerebral perfusion pressure (CPP). The effect of hyperbaric oxygen (HBO) on physiological and clinical outcomes after SAH, as well as the expressions of hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes, such as BNIP3 and VEGF was evaluated. Eighty-five male SD rats (300 to 350 g) were randomly assigned to sham, SAH, and SAH+HBO groups. Subarachnoid hemorrhage was induced by endovascular perforation. Cortical cerebral blood flow (CBF), ICP, brain water content, brain swelling, neurologic function, and mortality were assessed. HBO (100% O2, 2.8 ATA for 2 h) was initiated at 1 h after SAH. Rats were sacrificed at 24 h to harvest tissues for Western blot or for histology. Apoptotic morphology accompanied by strong immunostaining of HIF-1alpha, VEGF, and BNIP3 were observed in the hippocampus and the cortex after SAH. Increased expressions of HIF-1alpha, VEGF, and BNIP3 were quantified by Western blot. HBO reduced the expressions of HIF-1alpha, VEGF, and BNIP3, diminished neuronal damage and improved CBF and neurologic function. HBO reduced early brain injury after SAH, probably by inhibition of HIF-1alpha and its target genes, which led to the decrease of apoptosis and preservation of the blood-brain barrier function.
Ostrowski
Robert P
RP
Department of Physiology, Loma Linda University, Loma Linda, California, USA.
Colohan
Austin R T
AR
Zhang
John H
JH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019586:Intracranial Hypertension / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
C090121:BNIP3 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat