The effect of experimental ischaemia on the direct cortical response of the motor cortex in primates

We studied the changes in amplitude of the first short latency positive potential (2.3 +/- 0.3 msec, mean +/- S.D.) of the direct cortical response (DCR) elicited by surface electrical stimulation of the motor cortex in anaesthetised baboons. Local cortical blood flow, measured by the hydrogen clearance method, was progressively reduced by acute middle cerebral artery occlusion and subsequent hypotension and was related to the amplitude of this potential. With flow levels greater than 25 ml/100 g/min the DCR was essentially unaffected, but it was lost with flows below 20 ml/100 g/min. These results indicate a threshold relationship between the generation of the electrical activity evoked in the cortical elements and local cortical flow, similar to that previously demonstrated for cortical somatosensory evoked potentials.     

Cerebral blood flows and tissue oxygen levels associated with maintenance of the somatosensory evoked potential and cortical neuronal activity in focal ischemia

The middle cerebral artery was occluded in 18 cats to evaluate the physiological consequences of cerebral blood flow reductions on the somatosensory evoked potential, spontaneous neuronal activity, and oxygen availability in the ipsilateral and contralateral hemispheres. In the ipsilateral ectosylvian gyrus high-grade ischemia was produced as blood flow in the gray matter was reduced from 52.1 +/- 8.6 (mean +/- SE) to 13.3 +/- 9.0 ml/100 g/min and in the white matter from 33.8 +/- 5.6 to 6.1 +/- 6.4 ml/100 g/min. This significant reduction (p less than 0.05) was associated with abolition of the cortical component of the somatosensory evoked potentials. In all animals occlusion resulted in a predictable extended latency change and a variable amplitude response of the cortical component of the contralaterally recorded somatosensory evoked potentials. In 5 animals, oxygen availability was measured and spontaneous neuronal activity in the contralateral hemisphere was recorded. Volume expansion and hemodilution with either dextran or saline infusions elevated cerebral blood flow in the contralateral gray matter significantly (p less than 0.05) compared with the control and clip values. Ipsilateral spontaneous activity stopped within 4-12 minutes of occlusion, while contralateral spike activity persisted at rates at least equal to those recorded immediately following occlusion.     

Consistency of cerebral blood flow and evoked potential alterations with reversible focal ischemia in cats

To enhance the consistency of the ischemic insult caused by reversible transorbital middle cerebral artery occlusion, we investigated the variability of somatosensory evoked potential amplitudes and regional cerebral blood flow in 26 anesthetized cats using four procedures to induce transient ischemia. These procedures included 60 minutes of left middle cerebral artery occlusion with or without left common carotid artery occlusion and 120 minutes of left middle cerebral artery occlusion with or without bilateral common carotid artery occlusion. Blood flow in the left middle cerebral artery territory was markedly and consistently reduced to less than 20 ml/min/100 g with simultaneous occlusion of the left middle cerebral artery and both common carotid arteries. The standard deviation of blood flow with this procedure (5.4) was less than that with the other three procedures (13-25). The amplitudes of ipsilateral somatosensory evoked potentials were decreased to approximately 20% of control during ischemia with all four procedures. During reperfusion, amplitudes recovered more slowly, to half of control, after both procedures involving 120 minutes of ischemia. After 120 minutes of reperfusion, the range of amplitudes was smallest in the group exposed to middle cerebral artery occlusion with bilateral common carotid artery occlusion. The degree of recovery of the somatosensory evoked potentials correlated with residual blood flow in both the ipsilateral middle cerebral artery territory and in the white matter during ischemia. We conclude that the most consistent model of focal ischemia and reperfusion in cats in which there is partial recovery of somatosensory evoked potentials is occlusion of one middle cerebral artery and both common carotid arteries for 120 minutes.     

Anesthetic modulation of cerebral hemodynamic and evoked responses to transient middle cerebral artery occlusion in cats

We measured cerebral blood flow and somatosensory evoked potentials during transient focal cerebral ischemia in cats to compare the effects of four commonly used anesthetic regimens: ketamine/fentanyl/N2O (fentanyl), pentobarbital, ketamine/alpha-chloralose (alpha-chloralose), and ketamine/halothane/N2O (halothane). Six cats in each group were subjected to 60 minutes of left middle cerebral artery occlusion followed by 120 minutes of reperfusion. Although the amplitude of the initial somatosensory evoked potential wave complex was highest in the alpha-chloralose group (58.6 +/- 16.5 microV) and smallest in the halothane group (27.5 +/- 5.7 microV), amplitude fell by 75% in all groups upon occlusion. Baseline cerebral blood flow varied substantially between groups (e.g., in the right intersylvian gyrus: fentanyl, 96 +/- 12; pentobarbital, 30 +/- 5; alpha-chloralose, 24 +/- 3; and halothane, 76 +/- 11 ml/min/100 g). Occlusion decreased cerebral blood flow to subcortical (e.g., left caudate) structures in all groups (fentanyl, 29 +/- 11%; pentobabital, 45 +/- 12%; alpha-chloralose, 27 +/- 13%; and halothane, 18 +/- 5% of baseline). Postischemic hyperemia occurred in the cortical regions of cats anesthetized with pentobarbital or alpha-chloralose that had reduced cerebral blood flows during occlusion but not in cats anesthetized with fentanyl (cerebral blood flow during occlusion not different from that of cats anesthetized with pentobarbital or alpha-chloralose) or halothane. After 120 minutes of reperfusion, cerebral blood flow had returned to baseline values in all groups. Recovery of cerebral blood flow and somatosensory evoked potential amplitude at that time did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional impairment due to white matter ischemia after middle cerebral artery occlusion in cats

We recorded regional cerebral blood flow, somatosensory evoked potentials, and auditory evoked potentials in the thalamic relay nuclei (ventral posterior lateral nucleus and medial geniculate body) and in the somatosensory and auditory cortices during and after 1 hour of transient left middle cerebral artery occlusion in nine cats. Regional cerebral blood flow was also measured in the thalamocortical tracts of five of these cats. Additionally, the integrity of thalamocortical connections was tested by retrograde labeling of the thalamic nuclei with horseradish peroxidase in eight cats (three of which experienced no ischemia). Regional cerebral blood flow was severely reduced during middle cerebral artery occlusion in the left primary auditory cortex (8.5 ml/100 g/min) and in white matter pathways (6.4-7.6 ml/100 g/min). In contrast, regional cerebral blood flow did not change significantly in the somatosensory cortex or in either thalamic nucleus. Evoked potentials were abolished in both cortices but remained unchanged in the thalamic nuclei. Cortical somatosensory evoked potentials disappeared 5-8 minutes later than auditory evoked potentials. Recirculation after 1 hour of ischemia resulted in rapid and almost complete recovery (94%) of somatosensory evoked potentials and little recovery (18.4%) of auditory evoked potentials. We conclude that in the auditory pathway both cortical and fiber tract ischemia are (perhaps synergistically) responsible for dysfunction, while in the somatosensory cortex evoked potentials are abolished due to white matter ischemia. The delayed disappearance and better recovery of somatosensory than of auditory evoked potentials indicate that ischemic tolerance is higher in fiber tracts than in cortex.     

Neurofunctional disturbances as related to cortical ischemia and white matter ischemia

We evaluated regional cerebral blood flow (rCBF) by means of hydrogen clearance method as well as [14C]-iodoantipyrine autoradiographic method, cortical auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) induced by forelimb (median nerve) stimulation (SEP-F), and SEP induced by hindlimb (tibial nerve) stimulation (SEP-H) in cats after occlusion of the left middle cerebral artery (MCA) under alpha-chloralose anesthesia. According to the degree of ischemia, the experimental animals were divided into two groups. One was the critical ischemia which was defined as permanent total suppression of AEP, and low residual blood flow in the auditory cortex. And the other was the non-critical ischemia which included transient suppression and spontaneous recovery of the cortical sensory evoked potentials, and high residual blood flow (greater than 15 ml/100 g/min). In one cat with transient suppression of three kinds of sensory evoked potentials, the [14C]-iodoantipyrine (IAP) autoradiograph revealed only a limited ischemic area of subcortical white matter. In the critical ischemia group, ischemia of the primary sensory cortex ranged from the mostly affected primary auditory cortex (supplied by the MCA) to the least affected hindlimb projection area within primary somatosensory cortex (supplied by the ACA). The forelimb projection area of the primary somatosensory cortex (supplied by both ACA and MCA) showed a mild or moderate reduction of rCBF after occlusion. The [14C]-IAP autoradiograph showed severe reduction of the white matter including the somatosensory pathway in the wide range. However, rCBF in the thalamus and hindlimb projection area within somatosensory cortex was almost intact in the cat with ischemia.(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.     

Functional recovery of cortical neurons as related to degree and duration of ischemia

Simultaneous recordings of spontaneous single cell activity and local cerebral blood flow were obtained from 72 cortical neurons and adjacent brain in 54 cats before, during, and after ischemia induced by reversible occlusion of the middle cerebral artery. In most cells spontaneous electrical activity ceased at flow values of about 0.18 ml/gm/min (range, 0.06 to 0.22 ml/gm/min). No signal was obtained from 28 neurons during reperfusion following ischemia of varying degree and duration. Overall, neurons exposed to a residual flow of 0.14 ml/gm/min or less for more than 45 minutes had a poorer prognosis compared to any other combination of degree and duration of ischemia. A discriminant curve was estimated to define the border line between recovering and nonrecovering cells. Regions showing irreversible neuronal failure contained selective neuronal necrosis or areas of infarction by histological examination. Reperfusion restored neuronal function in 44 cells. In this group of neurons, there was a joint interaction of duration of ischemia, ischemic residual flow, and recovery time: cells exposed to moderate ischemia (0.09 to 0.22 ml/gm/min) for up to 20 minutes recovered rapidly; most neurons subjected either to extreme ischemia (less than 0.09 ml/gm/min) of short duration (less than 20 minutes) or to moderate ischemia (0.09 to 0.22 ml/gm/min) for longer periods (20 to 141 minutes) required from 19 to 50 minutes for recovery. A few resistant neurons tolerated less than 0.09 ml/gm/min for more than 20 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Chronic brain ischemia in the monkey assessed by somatosensory evoked potentials and local blood flow measurements

Physiological changes occurring in experimentally induced chronic ischemic areas of the brain in monkeys have been investigated by measuring local cerebral blood flow (lCBF) and recording somatosensory evoked potentials (SEPs) to median nerve stimulation in the cortex and thalamus (VPL). Ischemia was produced by occlusion of the middle cerebral artery (MCA). Its development was followed for weeks in the unanesthetized monkey. SEPs in VPL and cortex were shown to be useful indicators of neuronal activity in the course of brain ischemia. The most reliable parameters were found to be the amplitude of components P10, P12 and P20 of the cortical SEP, generated around the central sulcus. The relationship between the changes in spontaneous recovery of the SEPs, lCBF and behavioral signs, in the course of time, revealed characteristic patterns. Different components of the cortical SEP provide useful information on the localization of the ischemic cortical area. In addition, the amplitude of the VPL SEP may also change significantly after the occlusion of the MCA. Clear evidence for the phenomenon of diaschisis in terms of SEPs, was found in only one animal. An analysis of the relationship between lCBF and the amplitude of the SEPs showed that cortical SEPs could be measured at local CBF levels as low as 15 ml/100 g X min. The relationship between lCBF and cortical SEP amplitude was approximately linear in the range from about 60 ml/100 g X min down to 15 ml/100 g X min.     

Neurovascular coupling varies with level of global cerebral ischemia in a rat model

In this study, cerebral blood flow, oxygenation, metabolic, and electrical functional responses to forepaw stimulation were monitored in rats at different levels of global cerebral ischemia from mild to severe. Laser speckle contrast imaging and optical imaging of intrinsic signals were used to measure changes in blood flow and oxygenation, respectively, along with a compartmental model to calculate changes in oxygen metabolism from these measured changes. To characterize the electrical response to functional stimulation, we measured somatosensory evoked potentials (SEPs). Global graded ischemia was induced through unilateral carotid artery occlusion, bilateral carotid artery occlusion, bilateral carotid and right subclavian artery (SCA) occlusion, or carotid and SCA occlusion with negative lower body pressure. We found that the amplitude of the functional metabolic response remained tightly coupled to the amplitude of the SEP at all levels of ischemia observed. However, as the level of ischemia became more severe, the flow response was more strongly attenuated than the electrical response, suggesting that global ischemia was associated with an uncoupling between the functional flow and electrical responses.     

Deafferentation versus cortical ischemia in a rabbit model of middle cerebral artery occlusion

A two-site middle cerebral artery occlusion model in rabbits was developed. Platinum electrodes served for simultaneous recordings of regional cerebral blood flow, auditory evoked potentials, and electroencephalogram in the left and right auditory cortex and in the left medial geniculate body. Auditory evoked potentials and regional cerebral blood flow were also recorded in the subcortical white matter, and regional cerebral blood flow was recorded in the internal capsule. Distal segment occlusion of the middle cerebral artery caused severe cortical ischemia in four of 11 rabbits (Group I), accompanied by abolition of the auditory evoked potential in the left auditory cortex and white matter and severe reduction of the left electrocorticogram. Deep subcortical regions were affected either little or not at all. In the remaining seven rabbits (Group II) with only mild disturbance of cortical perfusion after distal middle cerebral artery occlusion, additional clamping of the proximal middle cerebral artery stem reduced thalamocortical tract blood flow and abolished cortical auditory evoked potentials. Spontaneous electrocorticogram was less affected in Group II than in Group I; thalamic regional cerebral blood flow and auditory evoked potentials were not altered. Histologically, ischemic lesions predominated in the cortex of Group I and in the subcortical structures of Group II rabbits. While correlated reductions in regional cerebral blood flow and auditory evoked potentials indicate effective cortical ischemia, the impairment of auditory evoked potentials in Group II rabbits must be due to cortical deafferentation by ischemia in the afferent tract. This model permits the investigation of the effects of predominantly cortical or subcortical ischemia in one functional system.     

Intracellular brain pH, indicator tissue perfusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit

Intracellular brain pH and indicator tissue perfusion were measured with a lipid-soluble, pH-sensitive fluorescent indicator in 10 rabbits who had either severe or moderate focal ischemia depending on whether the middle cerebral artery was occluded at its main trunk or bifurcation. Preocclusion tissue indicator perfusion was 50.1 ml/100 g/min and intracellular brain pH was 7.03. In severe focal ischemia, immediate postocclusion tissue perfusion was 12.7 ml/100 g/min and intracellular brain pH was 6.64. Four hours after occlusion, the perfusion was 5.2 ml/100 g/min and intracellular brain pH was 6.08. There was EEG and histological confirmation of infarction. In the moderate focal ischemia group, immediate postocclusion flow was 20.0 ml/100 g/min and intracellular brain pH was 6.92. At 3 h, postocclusion tissue perfusion was 22.6 ml/100 g/min and intracellular brain pH was 6.86. Therefore, for the first 3 h, this ischemic penumbra was stable. At the fourth hour, both cerebral tissue perfusion and intracellular brain pH worsened. This suggests that the ischemic penumbra is a dynamic state. The rabbit is a good experimental model for the production of both severe and moderate focal ischemia.     

Age-related differences in recovery of blood flow and metabolism after cerebral ischemia in swine

We tested two hypotheses: 1) that cerebral blood flow, oxygen consumption, and evoked potentials recover to preischemic values at 120 minutes of reperfusion more completely in 1-2-week-old piglets than in 6-10-month-old pigs after complete ischemia; and 2) that recovery of cerebral blood flow, oxygen consumption, and electrical function in piglets and pigs at 120 minutes of reperfusion is better after incomplete than after complete ischemia. During 30 minutes of ischemia produced by intracranial pressure elevation, cerebral blood flow determined by the microspheres technique was decreased to 0-1 ml/min/100 g with complete ischemia, to 1-10 ml/min/100 g with severe incomplete ischemia, or to 10-20 ml/min/100 g with moderate incomplete ischemia. During reperfusion after complete ischemia, both piglets and pigs demonstrated hyperemia but delayed hypoperfusion occurred in more brain regions in pigs, oxygen consumption returned to preischemic values in piglets but not in pigs (70 +/- 10% of preischemic values), and evoked potentials recovered better in piglets than in pigs (24 +/- 4% and 9 +/- 4% of preischemic values, respectively). Both piglets and pigs had fewer brain areas with hyperemia and hypoperfusion and improved oxygen consumption and electrical function during recovery from incomplete than from complete ischemia. We speculate that piglets tolerate complete ischemia better than pigs because of decreased reperfusion injury and that both groups recover better from incomplete than complete ischemia because of improved substrate supply during ischemia.     

Neuropathologic consequences of internal carotid artery occlusion and hemorrhagic hypotension in baboons

We studied eight anesthetized and physiologically monitored adult baboons (Papio cyanocephalus); four were subjected to hemorrhagic hypotension alone and four to hemorrhagic hypotension plus unilateral carotid artery occlusion. Cerebral blood flow was measured using xenon-133, the electroencephalogram was recorded using silver-silver chloride epidural electrodes, and histologic examination was carried out after perfusion-fixation. In the baboons subjected to hypotension alone (mean arterial blood pressure of 28 mm Hg) cerebral blood flow was 28.5 +/- 5.0 ml/100 g/min, whereas in the baboons subjected to hypotension plus unilateral carotid artery occlusion it was 21.8 +/- 1.8 ml/100 g/min at a mean arterial blood pressure of 27 mm Hg. There was no ischemic damage in the former group, but in the latter group there was necrosis in the arterial boundary zones of three baboons and in the distribution of the middle cerebral artery in one. We conclude that, when combined with hypotension, unilateral carotid artery occlusion may lead to hemodynamic ischemia accentuated in the arterial boundary zones of the ipsilateral cerebral hemisphere.     

Phenylephrine-induced hypertension reduces ischemia following middle cerebral artery occlusion in rats

We studied the influence of phenylephrine-induced hypertension on the area of ischemia during brief middle cerebral artery occlusion. Rats were anesthetized with 1.2 minimal alveolar concentration (MAC) isoflurane, and the middle cerebral artery was occluded via a subtemporal craniectomy. Immediately thereafter, in one group (n = 9) arterial blood pressure was increased 30-35 mm Hg above the preocclusion level by intravenous infusion of phenylephrine. In a second, control, group (n = 10) there was no manipulation of blood pressure. Local cerebral blood flow was determined autoradiographically 15 minutes after occlusion. The areas (expressed as a percentage of the total coronal cross-sectional area) in which local cerebral blood flow decreased to three ranges (0-6 ml/100 g/min [rapid neuronal death probable], 6-15 ml/100 g/min [delayed neuronal death probable], and 15-23 ml/100 g/min [electrophysiologic dysfunction with prolonged survival probable]) were measured. The areas in which local cerebral blood flow decreased to the two more severely ischemic ranges were smaller in the phenylephrine group than in the control group. For example, in the coronal section in the center of the middle cerebral artery distribution, local cerebral blood flow was 0-6 ml/100 g/min in 6.7 +/- 1.4% of the section in normotensive rats but was in that range in only 1.7 +/- 0.6% of the section during phenylephrine-induced hypertension (p less than 0.05). For the 6-15 ml/100 g/min range, the areas were 6.8 +/- 0.8% and 3.8 +/- 0.7%, respectively (p less than 0.05). For the 15-23 ml/100 g/min range, there were no differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibition of leukocyte function by administration of monoclonal antibody 60.3 (MoAb 60.3) improves electrophysiological recovery and decreases injury volume following transient focal cerebral ischemia in cats. METHODS: Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive either 2 mg/kg MoAb 60.3 (n = 8) directed at the CDw18 leukocyte antigen complex or an equal volume of diluent (sterile saline; n = 10) at 45 minutes of ischemia in a blinded fashion. RESULTS: Blood flow to the left temporoparietal cortex decreased to less than 5 ml/min/100 g with ischemia, but was minimally affected on the right side. Postischemic hyperemia occurred in the left caudate nucleus, whereas blood flow in other brain regions returned to control. No region demonstrated delayed hypoperfusion, and there were no differences between groups. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 10% of baseline amplitude at 180 minutes of reperfusion in both groups. Left hemispheric injury volume, as assessed by 2,3,5-triphenyltetrazolium chloride staining, was not affected by drug treatment (mean +/- SE values: MoAb 60.3, 37 +/- 5%; placebo, 38 +/- 7% of hemisphere). CONCLUSIONS: Inhibition of leukocyte function with MoAb 60.3 does not afford protection from severe focal ischemia and reperfusion in cats.     

Differences in ischemia-induced accumulation of amino acids in the cat cortex

It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.     

Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats.

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrical stimulation of motor cortex in experimental cortical ischaemia: pyramidal responses at C5 and the surface EMG.

In 7 baboons maintained under propofol anaesthesia, pyramidal tract responses were related to the corresponding peripheral EMG evoked by electrical stimulation of the motor cortex under conditions of focal cortical ischaemia. Pyramidal responses were recorded epidurally at the C5 level and the EMG was recorded from the contralateral hand or foot muscle using subdermal needle electrodes. Cortical ischaemia was produced by transorbital occlusion of the common anterior cerebral artery, and regional cortical blood flow was measured by the hydrogen clearance method. In the normally perfused brain, the later I waves of the C5 response required a lower stimulus strength to elicit them than the earlier I1 wave. It was more difficult to record the EMG from the hand than from the foot following stimulation of the corresponding cortex even though the C5 responses were always obtained in both cases. With moderate ischaemia, the later I waves were selectively abolished, leaving the D and I1 waves. EMG amplitude was significantly correlated with cortical blood flow (r = 0.88, P less than 0.005), and the threshold of cortical flow for the EMG was 10-13 ml/100 g/min. Our results indicate that changes in amplitude of the late I waves and particularly of the EMG are sensitive indicators of cortical ischaemia.