Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats
Document Type
Journal ArticlePublication Date
2007-09-01Keywords
AnimalsBrain
Brain Ischemia
Cell Death
Cerebrovascular Circulation
*Hyperoxia
Infarction, Middle Cerebral Artery
Magnetic Resonance Imaging
Male
Neurons
Oxygen Inhalation Therapy
Rats
Rats, Sprague-Dawley
Neurology
Metadata
Show full item recordAbstract
Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered for 3 h (P>0.05) and by 44% when administered for 6 h (P<0.05). In experiment 2, NBO acutely (390 mins, P<0.05) reduced in situ end labeling (ISEL) positivity in the ipsilesional penumbra but increased contralesional necrotic as well as caspase-3-mediated apoptotic cell death. In experiment 3, CBF characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the apparent diffusion coefficient (ADC)-derived lesion volume essentially stopped progressing during NBO treatment, resulting in a persistent PWI/DWI mismatch that could be salvaged by delayed (3 h) reperfusion. In conclusion, NBO (1) acutely preserved the perfusion/diffusion mismatch without altering CBF, (2) significantly extended the time window for reperfusion, (3) induced lasting neuroprotection in permanent ischemia, and (4) although capable of reducing cell death in hypoperfused tissue it also induced cell death in otherwise unaffected areas. Our data suggest that NBO may represent a promising strategy for acute stroke treatment.Source
J Cereb Blood Flow Metab. 2007 Sep;27(9):1632-42. Epub 2007 Feb 21. Link to article on publisher's siteDOI
10.1038/sj.jcbfm.9600463Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37578PubMed ID
17311078Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/sj.jcbfm.9600463