Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic 14C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25-94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.

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SUMMARY A method of quantitative autoradiography using M C-labelled 5,5-dimethyl-2,4-oxazolidinedione I4 C-DMO to evaluate the local changes in brain pH after ischemia is described. In normal control raU the calculated tissue pH values in gray matter were slightly lower than those in white matter, and there was no significant difference in the calculated pH among the various structures in cortical and subcortical gray matter. Four hours after a left middle cerebral artery (MCA) occlusion, marked reductions in M C-DMO concentrations were demonstrated in the anterior two-thirds of the cerebral cortex and in the lateral part of the caudate nucleus indicating tissue acidosis in these areas. Although several assumptions are required for the calculation of pH in brain tissue, this method would appear very useful in the investigation of the altered metabolic state In ischemlc brain. The applicability of "C-labelled DMO to positron emission tomography (PET) for the study of cerebral acid-base balance has recently been proposed. 10 Regional pH changes in the brain using quantitative autoradiography with I4 C-DMO have not been studied extensively, yet such a study could demonstrate regional pH, in normal brain and the changes that occur in it in diseased brain. This information could then be correlated with regional cerebral blood flow and metabolism.The purpose of this paper is to describe regional pH values of normal rat brain using quantitative autoradiography with I4 C-DMO. The same methodology is then applied to study pH changes in an ischemic model. Methodological problems and practical limitations are also discussed. Materials and Method General ProcedureSprague-Dawley rats (20O-250g) were used throughout the experiments. They were anesthetized with 1.5-2.0% halothane during cannulation of femoral artery and vein and during the occlusion of the middle cerebral artery. For all experiments I4 C-DMO (specific activity 55 mCi/rnmol; Amersham, Bucks, England) was dissolved in saline. Rats were allowed to awaken from anesthetic for 30 minutes before the start of U C-DMO infusions. During the experiments, the

SUMMARY The use of three sets of the double-tracer autoradiographic technique to measure topographical changes of local cerebral blood flow (LCBF), glucose utilization (LCGU), and tissue pH following a 3 h middle cerebral artery (MCA) occlusion in the rat is described.In a sham-operated group of animals there was 10% reduction of LCBF and 7% reduction of LCGU in the most affected areas as compared to the contralateral homologous regions. However, the ratio of LCGU/LCBF in the affected areas remained within normal limits.In the MCA-occluded animals, LCGU showed a bimodal response to decreased LCBF. LCGU decreased with reduced LCBF until LCBF fell to 38% of normal. Below this LCBF level LCGU increased, most likely implying anerobic glycolysis. Decline of tissue pH corresponds to the mismatch of LCBF and LCGU. These results suggest that brain tissue pH change cannot be predicted on the basis of LCBF or LCGU alone.

The effects on local cerebral blood flow (LCBF) and glucose utilisation (LCGU) of permanent, bilateral carotid artery ligation (BCAL) were studied in conscious Wistar rats. LCBF and LCGU were measured using quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose (14C-DG) techniques in 24 anatomically discrete regions of the brain. LCBF in the cerebral hemispheres 2.5 h (acute) after BCAL significantly decreased to 25-87% of the sham control, with the exception of the mammillary body. After acute BCAL, there was a heterogeneous accumulation of 14C-DG in the caudate nucleus and cerebral cortices. Only in the lateral geniculate body did LCGU significantly decrease after BCAL. One week (chronic) later, LCBF was significantly decreased in 15 (containing the caudate nucleus and all the cerebral cortices) of 24 structures. LCGU in ten (containing the caudate nucleus and all the cerebral cortices) of 24 structures after chronic BCAL significantly decreased to 66-77% of the sham control, except for regions with neuronal damage in which there was a heterogeneous uptake of 14C-DG. The ratio of LCBF/LCGU in chronic BCAL was unchanged in comparison with values in the corresponding sham-operated group. This model of acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism, is expected to become a pertinent tool for the neurophysiologist.