Cerebral blood flow, glucose utilization, and electrocorticograms following common carotid artery occlusion in gerbils

We designed this study to elucidate the relations between cerebral function and glucose metabolism during the early stage of ischemia. We induced focal cerebral ischemia in 28 gerbils by occluding the common carotid artery. We recorded electrocorticograms in 34 gerbils by positioning bipolar electrodes between the anterior and middle cerebral arteries. We related the electrocorticograms to local cerebral glucose utilization measured with [14C]2-deoxyglucose in half the gerbils. A characteristic pattern (a zone of markedly decreased [14C]2-deoxyglucose uptake surrounded by a narrow band of greatly increased uptake) was observed on the autoradiogram in nine of the 14 experimental gerbils (64%). An electrocorticogram recorded from such a band of increased uptake was characterized by transient suppression of electrical activity followed by partial or complete recovery, and local cerebral blood flow in gerbils showing this electrocorticographic type were variable (15.0-43.3 ml/100 g/min). An electrocorticogram recorded from the ischemic core and inner border of this band, even when [14C]2-deoxyglucose uptake was relatively high, was characterized by the complete disappearance of electrical activity just after occlusion; cerebral blood flow in gerbils that showed this electrocorticographic type were consistently less than 15.0 ml/100 g/min. Our investigation suggests that the transient disappearance of electrocorticographic activity in the periphery of ischemia, which has relatively high residual blood flow, may relate to the heterogeneity of glucose consumption during the early stage of ischemia.     

Rotational behavior in gerbils following unilateral common carotid artery ligation

Summary Unilateral cerebral infarctions are produced in 30–50% of all gerbils subjected to ipsilateral ligation of a common carotid artery. It has previously been shown that this infarction is associated with a major depletion of ipsilateral brain dopamine. The present studies characterize the spontaneous and drug-induced rotational behavior manifested by these animals and attempt to relate it to the functional activity of dopaminergic synapses. The tendency of animals to turn towards the side of the lesion 2–3 hours after surgery was found to correlate highly with the unilateral dopamine depletion observed after 24 hours. Two patterns of rotational responses were observed among animals showing symptoms that were treated with d-amphetamine or apomorphine; these could be correlated with mortality 24 hours after surgery.     

Repeated unilateral carotid occlusion in Mongolian gerbils: quantitative analysis of cortical neuronal loss

Summary To develop an experimental model which enables quantitative analysis of chronic neuronal loss in the cerebral cortex, repeated ischemic insult was performed using unilateral carotid artery occulusion in Mongolian gerbils. The effect of the time interval between the repeated ischemic insult on the survival rate of the animals and the amount of cortical neuronal loss were examined. The time course of the cortical neuronal damage in repeated ischemic insult was also studied. We repeated the occlusion four times; i.e., one 10-min and three 7-min occlusion (total 31 min of ischemia). The number of animals surviving for 3 weeks after the last biochemic insult was minimum (15.4%) for animals undergoing occlusions at 1-h intervals and maximum (100%) at 24- and 48-h intervals. The number of ischemic neuronal deaths was also dependent upon the time interval, and it was so pronounced as to allow analysis at intervals of 12 hr or 24 hr in the absence of infarction in the cortex. The number of neuronal deaths could not be determined for animals with occlusion at 1-h intervals due to the production of a large infarction, with which the 3-week survival rate was minimum. The temporal profile of cortical neuronal loss in the repeated ischemic insult at 24-h intervals indicated that the number of cortical neurons significantly decreased until 7 days after the start of the ischemic procedure. This model is useful for clarifying the pathophysiology of chronically developing ischemic neuronal death.     

Local cerebral blood flow during and after bilateral carotid artery occlusion in unanesthetized gerbils

Using [14C]iodoantipyrine autoradiography, we measured regional cerebral blood flow in unanesthetized gerbils subjected to 2 (n = 5) or 30 (n = 6) minutes of bilateral carotid artery occlusion or 5 (n = 6), 30 (n = 6), or 120 (n = 5) minutes of reflow after 30 minutes of occlusion. Blood pressure, respiratory rate, and blood gases were recorded, and these and other gerbils were evaluated with periodic neurologic examinations. Blood flow to structures above the level of the diencephalon ceased almost totally during occlusion. The lateral thalamus, the rostral three quarters of the hypothalamus, and the superior colliculi were also markedly ischemic. Blood flow to the brainstem and cerebellum was only slightly affected. After release of the occlusion, blood flow was restored in some of the affected areas but to levels somewhat below that in eight sham-operated gerbils. In several areas, principally column-shaped areas in the cortex as well as patchy areas in other structures, blood flow did not recover. This inhomogeneous blood flow distribution lasted at least 30 minutes after release of the occlusion. Thereafter, the inhomogeneity slowly disappeared in such a manner that blood flow to originally well reperfused areas appeared to decrease while that to poorly reperfused areas increased. During reflow, blood flow in the brainstem and cerebellum slowly and continuously decreased. We show that there is an early no-reflow phenomenon that is inhomogeneous and appears to be of vascular origin and lasts approximately 30 minutes after release of the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic threshold of brain protein synthesis after unilateral carotid artery occlusion in gerbils

The threshold of the relation between regional cerebral blood flow and regional cerebral protein synthesis was investigated in gerbils submitted to a 1-hour occlusion of the left common carotid artery. Blood flow was measured with [131I]iodoantipyrine and protein synthesis with [14C]leucine using double-tracer autoradiography and trichloroacetic acid wash-incubation for removal of nonincorporated tracer radioactivity. Specific activity of blood and brain leucine and [14C]leucine incorporation into brain proteins was also measured by conventional high-performance liquid chromatography to validate the autoradiographic approach. In control gerbils, gray matter blood flow ranged between 180 and 220 ml/100 g/min and fractional amino acid incorporation was approximately 80%. Unilateral carotid artery occlusion resulted in graded ischemia with blood flow between 10 and 100 ml/100 g/min. Regional cerebral protein synthesis gradually declined at blood flows of less than 100 ml/100 g/min and approached 0 at a blood flow of 40 ml/100 g/min. This threshold for complete suppression of protein synthesis is much higher than that for maintenance of tissue energy state and suggests that the size of an infarct after focal ischemia is determined by the suppression of protein synthesis rather than by the breakdown of energy metabolism.     

Hemispheric blood flow in the rat after unilateral common carotid occlusion: evolution with time

Acute occlusion of one common carotid artery in the anesthetized normocapnic rat results in a moderate cerebral blood flow (CBF) decrease in both cerebral hemispheres. No asymmetrical perfusion is observed when the overall flow in each hemisphere is considered. The increase in blood flow which normally occurs in hypercapnia is strongly impaired in the cerebral hemisphere on the occluded side resulting in an important asymmetrical hemispheric perfusion. The days (1, 5, 15, 30) following unilateral carotid occlusion normal control CBF values are found in both hemispheres in normocapnic conditions. Hemispheric perfusion asymmetry in hypercapnia also becomes progressively less pronounced with time but a slight asymmetry still persists one month after unilateral carotid occlusion.     

Prediction of stroke before and after unilateral occlusion of the common carotid artery in gerbils

A method was developed to predict the severity of cerebral ischemia before permanent occlusion of a common carotid artery in gerbils by observing the diameter and appearance of the artery after temporary occlusion and observing clinical signs after permanent occlusion. The severity of cerebral ischemia was confirmed by a sensitive immunohistochemical method and measurement of focal cerebral blood flow after 30 minutes' ischemia. All gerbils with greater than 40% reduction of the diameter and a white arterial margin distal to temporary occlusion developed severe neurologic signs following permanent occlusion, but no gerbils with reduction of less than 30% and a red arterial margin developed neurologic signs. With the cumulative neurologic score, gerbils could be divided into classes with no, mild, moderate, and severe symptoms, mostly after 10 minutes. Severely symptomatic gerbils were identified in 3 minutes. Extensive ischemic damage was observed in severely symptomatic gerbils, but no immunohistochemical lesion was detected in mildly symptomatic gerbils. Cerebral blood flow was markedly reduced in severely symptomatic gerbils but more selectively reduced in the cortical structures of moderately symptomatic gerbils. This prediction method is useful for investigating early cerebral ischemia and for evaluating the effectiveness of pharmacologic agents.     

Cerebral blood flow after carotid occlusion and extracranial-intracranial bypass.

Eleven patients with occlusion of one internal carotid artery showed marked reduction of regional cerebral blood flow (rCBF) through the hemisphere on the affected side with high rCBF on the opposite side. Six of the patients had no surgery, during follow-up of 2 to 5 years. rCBF increased on both sides leaving a persisting asymmetry of rCBF. Five patients had extracranial-intracranial bypass; rCBF increased on the affected side but not on the opposite side. Asymmetry of rCBF between the hemispheres remained but was much less than in the non-operated group.     

Cerebral blood flow and oxygen metabolism in symptomatic internal carotid artery occlusion by (traumatic) cervical artery dissection

The present study investigates whether cerebral infarction resulting from internal carotid artery occlusion by cervical dissection is due to emboli, released from a superimposed luminal thrombus, or is due to haemodynamic failure and hypoperfusion. Ten patients with a history of stroke and with a visible cerebral infarct on computed tomographic scan, due to cervical dissection and thrombosis of the internal carotid artery, were studied with positron emission tomography in order to assess the regional cerebral blood flow (rCBF), the regional cerebral metabolic rate of oxygen (rCMRO2) and the regional oxygen extraction fraction (rOEF) in different regions of the brain. rCBF and rCMRO2 were only decreased in the infarct area but not in the peri-infarct zone or elsewhere in the brain. As rOEF was not increased in the affected cerebral hemisphere, the present study suggests artery-to-artery embolism rather than a haemodynamic event as the cause of the stroke. Use of anticoagulants thus appears to be the appropriate treatment in the acute stage.     

Role of collateral flow on cerebral hemodynamics in patients with unilateral internal carotid artery occlusion

The objective of this study was to evaluate the role of collateral blood flow via the anterior and posterior communicating arteries (ACoA and PCoA) and via the ophthalmic artery (OphA) on cerebral hemodynamics, metabolism, and border zone infarcts in 57 patients with unilateral symptomatic occlusions of the internal carotid artery. Collateral flow via the ACoA and PCoA was determined with magnetic resonance angiography (MRA) and collateral flow via the OphA with transcranial Doppler (TCD). Volume flow was studied with MRA, metabolism with ¹H MR spectroscopy, CO₂ reactivity with TCD, and the incidence of border zone infarcts with MRI. Compared with controls, patients had deteriorated volume flow, metabolism, and CO₂ reactivity. No differences were found between patients with and patients without collateral flow through the ACoA and/or PCoA, or between patients with or without collateral flow via the OphA. Patients without collateral flow via any of these collaterals had decreased volume flow in the middle cerebral artery, decreased N -acetylaspartate/choline, and increased lactate/ N -acetylaspartate, compared with the other patients. Patients with symptomatic internal carotid artery occlusion have deteriorated cerebral hemodynamics and metabolism. Different collateral flow patterns via the ACoA, PCoA, or OphA have no effect on the hemodynamic and metabolic parameters, as long as one of these pathways is present.     

Critical cerebral blood flow for production of hemiparesis after unilateral carotid occlusion in the gerbil.

Transient cerebral ischaemia, produced by temporary unilateral common carotid artery (CCA) occlusion, was studied in the gerbil by means of chronically implanted hydrogen electrodes. Unilateral CCA occlusion produced behavioural signs of neurological deficit only when regional cerebral blood flow values in the ipsilateral cerebral hemisphere fell below a critical range of 0.20-0.22 ml/gm brain/min. Postischaemic poor perfusion (no-reflow) was an infrequent observation after removal of CCA occlusion.     

Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

[14C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion.     

Long-term video-EEG recordings following transient unilateral middle cerebral and common carotid artery occlusion in Long-Evans rats

The mechanisms of injured brain that establish poststroke seizures and epilepsy are not well understood, largely because animal modeling of these phenomena has had limited development. We studied the electrobehavioral properties of 2.5-month-old male Long-Evans rats by video-electroencephalogram (EEG) recordings during the 6 months following sham operation or lesioning by transient unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAO). The main findings of this study were: (1) control animals demonstrated interictal focal or restricted bilateral 7-8 Hz spike-wave discharges (SWDs) lasting 1-2 s without behavioral change and ictal generalized 7-8 Hz SWDs (absence seizures), which were prolonged, frequent, and associated with motor arrest of the animal; (2) lesioned animals demonstrated cortical infarction associated with interictal SWDs similar to controls, except that focal discharges were more numerous relative to bilateral discharges, and ictal SWDs, which were of shorter duration and less frequent than those of controls; (3) lesioned animals demonstrated decreased hemispheric and regional spectral power at approximately 7 and 15 Hz compared with controls, directly related to the reduced occurrence of ictal SWDs; and (4) lesioning did not independently generate either focal or generalized epileptic seizures. These studies demonstrate distinct electrobehavioral properties of Long-Evans rats lesioned by MCA/CCAO as juveniles and monitored by video-EEG recordings during young adulthood but fail to provide evidence of poststroke seizures or epilepsy.