Cerebral Artery Occlusion In Cats Research Articles

Time course of trace of diffusion tensor [Trace(D)] and histology in brain edema.

We examined the correlation between changes in the trace of diffusion tensor [Trace(D)], regional water content and tissue ultrastructure relating to cellular (cytotoxic) and vasogenic brain edema. Cellular edema was induced by left middle cerebral artery occlusion in cats (Kuroiwa T et al., 1998). Vasogenic edema was induced in the white matter of cats by a cold lesion (Kuroiwa T et al., 1999). In cellular edema, the water content increase correlated linearly with the Trace(D) decrease in both the gray and white matter. However, both the slopes and intercepts of the correlation lines were significantly different. Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendrocytic and myelinated axonal swelling were observed. In vasogenic edema, the increase in Trace(D) showed a significant linear correlation with the increase in tissue water content. Histologically, nerve fibers were dissociated and the extracellular space was markedly enlarged with protein-rich fluid. These result showed that the different slopes and intercepts of the water content--Trace(D) correlation lines for different subtype of brain edema, which reflect different ultrastructural localization of water, should be taken into account when evaluating brain edema using Trace(D) mapping.

Correlation of the average water diffusion constant with cerebral blood flow and ischemic damage after transient middle cerebral artery occlusion in cats.

Magnetic resonance water diffusion imaging can detect early ischemic changes in stroke. Using a middle cerebral artery occlusion model, we examined which range of values of the orientation-independent diffusion quantity Dav = 1/3Trace(D) = 1/3(Dxx + Dyy + Dzz) is an early noninvasive indicator of reduced cerebral perfusion and focal brain injury. Cats underwent either a 30-min occlusion followed by 3.5 h reperfusion (n = 7) or a 60-min occlusion followed by 4-h reperfusion (n = 6). Repeated measurements of CBF were made with radiolabeled microspheres, and acute focal injury was measured with triphenyltetrazolium chloride (TTC) staining. During occlusion, the decrease in Dav correlated with CBF for caudate [30-min occlusion (n = 13): p < 0.0001: 60-min occlusion (n = 6): p < 0.02] and for cortex [30-min occlusion (n = 12): p < 0.0001: 60-min occlusion (n = 5): p < 0.04]. Variable caudate and hemispheric injury levels were found among cats in both groups. The area of tissue injury demarcated by TTC began to correlate with the area of reduced Dav by 30 min of occlusion (p < 0.02), and this correlation improved (p < 0.0001) at 1, 1.5, and 2.0 h after the onset of occlusion. The time necessary to reach a one-to-one correspondence between the percent of hemisphere injured and the percent of hemispheric area with Dav < 0.65 x 10(-9) m2/s was 2 h after occlusion. Thus, the absolute value of Dav is a good indicator of the risk of tissue injury, whereas the combination of Dav and the length of time of Dav reduction is an excellent predictor of acute focal tissue injury demarcated by TTC staining.

Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats.

Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. Final infarct size was determined on serial histologic sections. In the areas of final glucose metabolic depression that were slightly larger than the histologic infarcts, mean CBF dropped to approximately 40% of control values immediately on arterial occlusion. If further decreased to < 20% during the course of the experiment. This progressive ischemia was most conspicuous in border zones. CMRO2 fell to a lesser degree (55%), eventually reaching approximately 25% of its control level. At early stages, OEF increased mainly in the center of ischemia. With time, areas of increased OEF moved from the center to the periphery of the MCA territory. Concurrently, progressive secondary decreases in OEF in conjunction with further reductions of CBF and CMRO2 indicated the development of central necrosis. The findings are highly suggestive of a dynamic penumbra. In five cats with complete MCA infarcts, CBF decreased and OEF increased in the contralateral hemisphere after 24 h, suggesting whole-brain damage. This effect may be explained by the widespread brain edema found histologically in addition to the nonspecific CBF reductions and OEF elevations observed also in the sham-operated controls after 1 day in the experimental condition. In one cat, cortical OEF increased only transiently. Normal CMRO2 and CMRglc were eventually restored, and the final infarct was small. This study demonstrates that acute regional pathophysiologic changes can be repeatedly assessed by multivariate PET in cats. Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.

O-197 - Effects of AE0047, a calcium antagonist, on cerebral circulation and brain edema formation after middle cerebral artery occlusion in cats.

O-197 - Effects of AE0047, a calcium antagonist, on cerebral circulation and brain edema formation after middle cerebral artery occlusion in cats.

Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats.

We tested the hypothesis that inhibition of nitric oxide synthase activity in brain before ischemia alters cerebral blood flow and decreases brain injury after 4 hours of middle cerebral artery occlusion in cats. Halothane-anesthetized cats underwent 4 hours of left middle cerebral artery occlusion after they were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester, at a dose that completely inhibited cortical nitric oxide synthase activity (10 mg/kg, n = 10), or an equal volume of diluent (10 mL saline, n = 10). Serial blood flow measurements were made with radiolabeled microspheres, and injury volume was measured by triphenyltetrazolium staining. Blood flow to caudate nucleus and inferior temporal cortex decreased to the same extent in both groups during middle cerebral artery occlusion. Somatosensory evoked potential amplitude was reduced to less than 10% of baseline values in both groups. Injury volume of ipsilateral caudate nucleus in cats pretreated with nitroarginine (52 +/- 5%, mean +/- SE) was less (P < .05) compared with the saline group (80 +/- 4%), whereas ipsilateral cerebral hemispheric injury volume was similar between the two groups (30 +/- 6% and 32 +/- 4% of hemisphere in saline and nitroarginine groups, respectively). These results suggest that inhibition of nitric oxide synthase decreases caudate injury volume at 4 hours of middle cerebral artery occlusion without an alteration in distribution of cerebral blood flow.

The effect of a new calcium antagonist, TA3090 (clentiazem), on experimental transient focal cerebral ischemia in cats.

TA3090 (Clentiazem) has been shown to have cerebrovascular protective properties in three experimental studies. An in vivo investigation was undertaken to determine its effects on pial arteries and cerebral blood flow and its therapeutic value in transient focal cerebral ischemia. This experiment was divided into two protocols. In the first, 200 or 400 micrograms/kg per hour TA3090 was administered continuously for 3 hours in cats without ischemic insult (n = 6 for each group). The effects on pial arteries and cerebral blood flow were estimated. In the second protocol, 400 micrograms/kg per hour TA3090 (treated group, n = 14) or physiological saline (control group, n = 10) was administered 5 minutes before 1 hour of middle cerebral artery occlusion in cats. The effects on the pial arteries and cerebral blood flow were observed continuously, followed by autoradiography for a quantitative measurement of cerebral blood flow 5 hours after middle cerebral artery recirculation. The volumes of the cerebral edema and infarct were estimated by planimetry from cerebral preparations made for histological examination. Pial arteries dilated by up to approximately 10% in the 400-micrograms group and 3% in the 200-micrograms group 30 minutes after administration of TA3090. Increases in cerebral blood flow of about 10% in the 400-micrograms group and 2% in the 200-micrograms group were demonstrated with laser Doppler flowmetry. In the second protocol, dilatation of pial arteries was significantly smaller during and after the ischemic insult in the treated group compared with the control group (p < 0.01). Cerebral blood flow decreased less significantly during ischemia (p < 0.01 at the end of ischemia) and increased less significantly after ischemia (p < 0.01 at the end) in the treated group compared with the control group. Autoradiography showed a more remarkable increase in cerebral blood flow due to luxury perfusion in the cerebral cortex, which was mainly perfused by the middle cerebral artery on the affected side in the control group (p < 0.01). Cerebral blood flow in the cerebral cortex, thalamus, and caudate nucleus on the contralateral side of the treated group increased by about 20% more than that of the control group (p < 0.05). Cerebral edema and infarction were much smaller in the treated group than in the control group (p < 0.01). 1) TA3090 dilates pial arteries and increases cerebral blood flow in normal brain regions in a dose-response fashion; 2) in ischemic regions compared with those in untreated animals, TA3090 results in a lesser reduction of cerebral blood flow during ischemia and in a lesser degree of hyperemia during reperfusion; 3) TA3090 is associated with less pial artery dilatation during ischemia, presumably due to improved collateral flow; and 4) the improved hemodynamic state with TA3090 is associated with significant reduction of cerebral edema and infarct size.

Neurologic and histologic evaluation of almitrine + raubasine (Duxil®) in middle cerebral artery occlusion in cats

Impairment of energy metabolism is the fundamental mechanism leading to cell death in ischemia. Using the middle cerebral artery (MCA) occlusion model in cats, we studied the effect of Duxil® (almitrine and raubasine combination), which was given either before and after or only after MCA occlusion, on ischemia in terms of neurological function and histological changes. Neurological function was assessed consecutively for 7 days after MCA occlusion using a categorical rating scale in 18 cats. Neurological function was significantly improved in treated animals than in non-treated controls regarding to the motor and sensory function, walking, posture and stepping reflex. Animals were killed on the 8th day and histological changes were examined by light and electron microscopies. Significant improvement in the morphological scores based on the light-microscopy changes were found in animals treated with Duxil® compared to non-treated ones. Under the electron microscopy, the protective effects of Duxil® were characterized by retaining glycogen and mitochondria. Morphological improvement was associated with the recovery of neurological function and especially profound in penumbra areas of MCA infarction. These results suggest that Duxil® has a protective effect against ischemic damage induced by occlusion of MCA in cats.

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.

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)

Fatal strokes in hyperglycemic cats.

Hyperglycemia is associated with three- to fourfold larger infarcts than normoglycemia following permanent middle cerebral artery occlusion in cats. We investigated the effects of glycemia on brain outcome when middle cerebral artery blood flow was restored (clip release) after 4 hours of occlusion. Seven of 13 hyperglycemic (22 mM) and one of 12 normoglycemic (6 mM) anesthetized cats developed total middle cerebral artery territory infarcts and hemispheric edema and died of brainstem compression. The remaining six and 11 cats recovered fully and later showed no or only small infarcts. Compared with permanent occlusion, restoration of blood flow after 4 hours reduced infarct volume in all normoglycemic and hyperglycemic cats that survived, but caused a much higher proportion (54% vs. 17%) of hyperglycemic and, for the first time, one normoglycemic cat, to die of infarct extension, hemorrhagic infarct conversion, and total territory edema. Thus, clip release after 4 hours caused some cats to show reduced and others to show augmented tissue damage. Rendering cats hyperglycemic substantially worsened their outcome after reperfusion by increasing their death rate from total territory edema sevenfold. Our results demonstrate that risk/benefit analyses for recanalization efforts in humans should take serum glucose concentrations into account.

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.

Effect of the ganglioside GM1 on neurologic function, electroencephalogram amplitude, and histology in chronic middle cerebral artery occlusion in cats.

The effect of the ganglioside GM1 on amplitude of the electroencephalogram, neurologic function, and histology has been studied in chronic middle cerebral artery occlusion in cats. Ischemia was produced by a 2-hour occlusion of the left middle cerebral artery and was followed by a 7-day observation period. GM1 was intravenously administered 30 minutes after occlusion and daily during the observation period. Using the reduction in the electroencephalogram amplitude to measure stroke severity, three cats with mild, three cats with moderate, and three cats with severe stroke were treated with 5 mg/kg GM1. Nine cats, three in each group, were treated with 30 mg/kg GM1, while nine cats, three in each group, received middle cerebral artery occlusion but no treatment. In all cats there was a precipitous fall in mean electroencephalogram amplitude during occlusion, followed by a secondary fall during the observation period. Treated cats showed better recovery of electroencephalogram amplitude during the first 4 hours of reperfusion and a smaller secondary fall than untreated cats. Treated cats, especially those treated with 5 mg/kg GM1, showed significant recovery of neurologic deficits compared with untreated cats. Histologic damage was less in treated cats than in untreated cats. Some cats treated with 30 mg/kg GM1 exhibited convulsions, whereas no untreated cat showed any seizure activity. Our findings suggest that gangliosides may improve the recovery of both neurologic deficits and morphologic damage in the central nervous system. These positive effects might be tentatively explained by stimulation of enzymatic activities such as Na+, K+-ATPase and adenyl cyclase.

Effect of treatment with fluosol and mannitol during temporary middle cerebral artery occlusion in cats.

Four groups of seven cats each were subjected to 6 hours of temporary middle cerebral artery (MCA) occlusion followed by reperfusion. During the first 30 minutes of the occlusion, Group 1 received 20% Fluosol-DA (FDA) and Group 2 received 20% FDA and mannitol; Group 3 received 20% FDA and mannitol 30 minutes before the occlusion, and Group 4 (control) received an infusion of saline solution during the first 30 minutes of occlusion. All cats breathed 100% oxygen throughout the occlusion and during 2 hours of reperfusion. Blood pressure, PaO2, and pH remained stable for 8 hours. PaO2 increased from an average base line level of 102 +/- 15 (SD) torr to 520 +/- 45 torr in Group 1, 450 +/- 41 torr in Group 2, 480 +/- 28 torr in Group 3, and 396 +/- 151 torr in Group 4 during the administration of 100% oxygen. The average fluorocrit during occlusion was 6% in Groups 1, 2, and 3. The 24-hour mortality rate was 71% in Group 1, 43% in Group 2, 29% in Group 3, and 14% in Group 4; a midline shift and herniation were present after each fatal infarct. The survivors were sacrificed 10 days after the occlusion. There was a trend toward improvement of neurological function at sacrifice in Groups 2 and 3 compared with Groups 1 and 4. The infarct areas on coronal sections were 2.4 times larger in Group 1 (FDA only) than in Group 4 (control) (P less than 0.05). There was no significant difference in infarct size between Group 4 and Group 2 or 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of treatment with fluosol and mannitol during temporary middle cerebral artery occlusion in cats

Effect of treatment with fluosol and mannitol during temporary middle cerebral artery occlusion in cats

Hyperglycemia enlarges infarct size in cerebrovascular occlusion in cats.

We investigated the influence of serum glucose concentration on infarct size following middle cerebral artery occlusion in cats. These animals were deprived of food for 48 hours and infused with 1) saline for 1 hour before and 8 hours after occlusion (n = 8), 2) 10% glucose solution for 1 hour before and 6 hours after occlusion and saline for 2 additional hours (n = 8), or 3) 10% glucose for 1 hour before and saline for 8 hours after occlusion (n = 5). Nineteen cats killed after 2 weeks' survival were subjected to morphometric infarct size determinations. Eight normoglycemic and 11 hyperglycemic cats exhibited infarcts affecting 10.2 +/- 3.4% and 29.5 +/- 6.5% (mean +/- SEM) of their middle cerebral artery territories, respectively (p less than 0.02). Cats of the two hyperglycemic groups showed similarly sized infarcts. However, two of eight (25%) of cats with preocclusion and postocclusion hyperglycemia died 8 and 24 hours after occlusion with infarction of the entire middle cerebral artery territory, marked hemispheral edema, and brainstem compression. Our results demonstrate that serum glucose concentration at the time of large cerebral vessel occlusion influences stroke outcome.

Experimental focal ischemia in cats: changes in multimodality evoked potentials as related to local cerebral blood flow and ischemic brain edema.

Somatosensory and auditory evoked cortical potentials (SEP's and AEP's), regional cerebral blood flow, regional brain water content, and alteration of the blood-brain barrier were investigated in 3 cortical areas during permanent and 1- and 2-hour transient occlusion of the left middle cerebral artery and after restoration of blood flow in cats. During occlusion, blood flow in the auditory cortex was severely suppressed. In the fore limb projection area of the somatosensory cortex, blood flow was moderately reduced while it was nearly unaffected in the hind limb projection area. Despite different degrees of ischemia in the 3 cortical areas, all evoked responses were completely abolished within 10 minutes after occlusion. During permanent occlusion, the pattern of blood flow reduction persisted, and all evoked potentials stayed abolished. Recirculation after occlusion restored blood flow rapidly. AEP's recovered poorly after both 1 and 2 hours of ischemia. SEP's regained normal amplitudes soon after recirculation in the group with 1-hour occlusion. After 2 hours of ischemia, the recovery of SEP's was variable but better than that of the AEP's. Remarkable water accumulation was observed in the auditory cortex of all 3 groups and was accompanied in the 2-hour ischemia group by a disruption of the blood-brain barrier. In the 2-hour group, water accumulation was also found in the subcortical white matter radiation, whereas significant changes in regional water content were not observed in the somatosensory areas. The present study indicates that abolition of SEP's during middle cerebral artery occlusion in cats is caused by lesions in the afferent pathway leading to cortical deafferentation rather than by cortical ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Flow-Metabolism Couple following Middle Cerebral Artery Occlusion in Cats

The regional flow-metabolism couple was studied during the recovery period after 1 h of left middle cerebral artery (MCA) occlusion in cats. Local CBF (LCBF) was assessed at the end of ischemia as well as at the end of 4 h of recirculation by the microsphere technique. Local CMRgl (LCMRgl) was measured at the end of the recirculation period with [14C]2-deoxyglucose. Histology was evaluated by light microscopy from coronal brain blocks adjacent to those used for the determination of LCBF and LCMRgl. When LCBF in the central and peripheral MCA territories during the recovery period was between 40 and 115% of the value in sham occlusion studies, LCMRgl was greater than the control level found in the sham studies, and was accompanied by slight histological damage. This finding suggests that anaerobic glycolysis may persist after transient ischemia in spite of the recovery of LCBF to a level that is normally greater than the threshold for the activation of anaerobic glycolysis (less than 40% of the control). Persistent anaerobic glycolysis in the reperfusion period following an ischemic insult may be a sign of early tissue damage. Some of the regions in the peripheral MCA territory with LCBF between 40 and 110% of the levels during the recovery period in the sham studies showed a mild to moderate depression in LCMRgl so that the flow-metabolism ratio remained normal. These regions did not exhibit histological damage. This possible protective mechanism of the tissue in response to ischemia is discussed from the standpoint of the relationship between flow and metabolism.

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats. Effects of anesthesia.

Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p less than 0.05). This was noted in densely areas (indomethacin = 84.3%, control = 87.5%), "penumbra" regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p less than 0.05), as was cerebral perfusion (p less than 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p less than 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p less than 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbital-stabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.

Multiparametric Imaging of Blood Flow and Metabolism after Middle Cerebral Artery Occlusion in Cats

In anesthetized adult cats, acute stroke was produced by transorbital occlusion of the left middle cerebral artery. A battery of imaging techniques was used for simultaneous evaluation of regional blood flow, glucose utilization, protein synthesis, pH, and the regional tissue content of glucose, ATP, and potassium. The electrophysiological impact of stroke was monitored by EEG frequency analysis and recording of somatosensory evoked potentials. Two hours after vascular occlusion, a close correlation existed between the degree of electrophysiological changes and biochemical alterations, in particular with the extent of tissue acidosis, ATP depletion, decrease of tissue potassium content, and suppression of protein synthesis. However, there was only a poor correlation with blood flow and glucose utilization. Both of these exhibited a greatly inhomogeneous pattern with regions of reduced, normal, or increased rates. In areas remote from the infarct, the content of biochemical substrates was normal but blood flow was reduced globally by approximately 50% and glucose utilization by approximately 20%. An anatomically defined regional pattern of cerebral or cerebellar diaschisis was not observed. It is concluded that during the acute phase of stroke, imaging of blood flow and glucose utilization does not provide an accurate estimate of the actual functional or metabolic disturbance. For the clinical evaluation of the development or treatment of stroke, in consequence, alternative noninvasive techniques such as imaging of protein synthesis and/or pH may be more relevant.

Neuronal injury following permanent middle cerebral artery occlusion in cats.

The border of a chronic infarct is sharply demarcated. We found in our investigation, however, that this is merely a macroscopic diagnosis and does not say anything about the structure of the tissue and the content of morphologically preserved neurons in the marginal zones. In six cats the left cerebral artery was permanently occluded. Eight weeks later the animals were killed and autoradiographic investigations were conducted on cryostat sections to determine rCBF. Adjacent to every 20-microns section, a 10-microns HE section was prepared. Preserved nerve cells were counted in several areas of the cortex in a symmetric fashion in both the infarcted and the contralateral side in the identical regions where rCBF had been measured in the preceding section. Two additional non-ischemic cat brains served as controls, which were investigated in the same manner as described above. A marked loss of neurons was observed in the border zone of the infarct. Only occasionally preserved ganglion cells were seen in each cortical layer. Even in areas one gyrus distant to the margin of the infarct the number of neurons was still reduced by one third as compared to the contralateral side. Starting only with the lateral gyrus the number of ganglionic cells was found to be equal on both sides.