Regional cerebral blood flow during hypoxia-ischemia in the immature rat: comparison of iodoantipyrine and iodoamphetamine as radioactive tracers

Abstract

The indicator fractionation method was used to measure regional cerebral blood flow (rCBF) in immature rats, using either iodo-[ 14C]antipyrine (IAP) or isopropyl-[ 14C]iodoamphetamine (IPIA) as the radioisotope. Seven-day postnatal rats received a subcutaneous injection of either IAP (5 μCi) of IPIA (10 μCi), two minutes following which the animals were sacrificed and their brains prepared for quantitative autoradiography. Blood flows to cerebral cortex, hippocampus, striatum, thalamus and hypothalamus were comparable using the two methods, whereas blood flows to white matter structures were substantially higher (+ 64–85%) with IAP. Spatial resolution, especially of the gray matter structures, was greater with IPIA than with IAP. During cerebral hypoxia-ischemia (unilateral common carotid artery ligation and hypoxia with 8% oxygen), blood flows to all regions of the ipsilateral cerebral hemisphere were not different from control at 10 and 20 min. At 1–3 h of hypoxia-ischemia, blood flows were decreased in all analyzed structures of the cerebral hemisphere ipsilateral to the carotid artery occlusion, ranging from 7% to 40% of control values. A columnar or patchy distribution of preferential perfusion was seen within the cerebral cortex, striatum and thalamus, with IPIA, which corresponds closely to the pathologic pattern of injury seen within these structures of the immature rat. Such a preferential perfusion was not seen in hippocampus, in which metabolic factors (intrinsic vulnerability) most likely predict the distribution of hypoxic-ischemic brain damage.