Pathogenesis of hypoxic-ischemic brain injury in a perinatal rodent model

Exposure of immature rats to 8% oxygen after unilateral carotid artery ligation (UCL) causes metabolic, neurochemical and histopathological changes in the ipsilateral forebrain that resemble those in human perinatal hypoxic-ischemic encephalopathy. Regional cerebral perfusion in this model was examined by visual analysis of India ink trapped in cerebral vessels and measurement of [14C]iodoantipyrine [( 14C]IAP) and [3H]flunitrazepam extraction into the brain. UCL alone reduced [14C]IAP accumulation in the ipsilateral hemisphere by 20% and hypoxia superimposed on UCL progressively reduced ipsilateral hemisphere perfusion by 71% at 2 h. Hypoxia probably injures neurons in this model by causing a critical reduction in cerebral perfusion, an effect which also appears to be important in the human disorder.