Focal Cerebral Ischemia In Cats Research Articles

Effects of hypothermia and rewarming on evoked potentials during transient focal cerebral ischemia in cats

We examined the effects of mild to moderate hypothermia and the influence of rewarming on electrophysiological function using somatosensory evoked potentials (SEPs) in transient focal ischemia in the brain. Nineteen cats underwent 60 min of left middle cerebral artery occlusion under normothermic (36 ° -37 ° C, n = 6) or hypothermic (30 ° -31 ° C, n = 13) conditions followed by 300 min of reperfusion with slow (120 min, n = 6) or rapid (30 min, n = 7) rewarming. Whole-body hypothermia was induced during ischemia and the first 180 min of reperfusion. SEPs and regional cerebral blood flow were measured before and during ischemia and during reperfusion. The specific gravity of gray and white matter was examined as the indicator of edema. During rewarming, SEP amplitudes recovered gradually. After rewarming, SEPs in the normothermic and rapid rewarming groups remained depressed (20%-40% of pre-occlusion values); however, recovery of SEPs was significantly enhanced in the slow rewarming group (p < 0.05). Hypothermia followed by slow rewarming reduced edema in gray and white matter. Rapid rewarming did not reduce edema in the white matter. The recovery of SEPs correlated with the extent of brain edema in transient focal ischemia. Rapid rewarming reduced the protective effect of hypothermia. [Neurol Res 2002; 24: 621-626]

Calcium ion transients in peri-infarct depolarizations may deteriorate ion homeostasis and expand infarction in focal cerebral ischemia in cats.

Harmful effects of peri-infarct depolarizations (PIDs) may depend on recurrent Ca(2+) influx. Thus far, few studies have documented the relevance of PIDs in gyrencephalic animals, and the progressive nature of this process has not been investigated over extended periods. We therefore studied in prolonged focal ischemia in cats spatial and temporal profiles of extracellular calcium ([Ca(2+)](o)) shifts in relation to direct current (DC) potential, nitric oxide (NO) concentration and regional cerebral blood flow alterations, and final pathological outcome. In halothane-anesthetized cats receiving either vehicle (n=12) or MK-801 treatment (5 mg/kg IV; n=10), the left middle cerebral artery was permanently occluded. Laser-Doppler probes, ion-selective microelectrodes, and NO electrodes measured simultaneously regional cerebral blood flow, DC potential, electrocorticogram, [Ca(2+)](o), and NO concentrations in ectosylvian and suprasylvian gyri of the left cerebral cortex. Persistent depolarization immediately after middle cerebral artery occlusion occurred in 10 ectosylvian and 4 suprasylvian gyri of vehicle-treated animals and in 9 ectosylvian and 3 suprasylvian gyri of MK-801-treated animals. PIDs associated with transient decreases of [Ca(2+)](o) were detected in suprasylvian gyri of only 4 vehicle-treated animals, of which 3 developed recurrent PIDs. Electrocorticogram was suppressed during PIDs, and electrocorticogram recovery worsened in a stepwise manner with consecutive depolarizations. PID duration increased slightly with ongoing ischemia and evolved to persistent depolarization at a final stage. NO transients were not detected during PID, and regional cerebral blood flow transients were not pronounced. Infarction was larger with initial persistent depolarization than with PID and was smallest in MK-801-treated animals. PID is not a common finding in peri-infarct zones in cats, and it is suppressed by the N:-methyl-D-aspartate antagonist MK-801. However, if repeated PIDs are generated, they result in a stepwise, progressive breakdown of neuronal function and ion homeostasis, probably contributing to the growth of infarction in focal cerebral ischemia. Recurrent Ca(2+) influx is a mechanism that presumably contributes to this process.

Administration of Selective Endothelin Receptor Type a Antagonist Ro 61-1790 Does Not Improve Outcome in Focal Cerebral Ischemia in Cat

The authors examined the effect of selective endothelin (ET) receptor type A (ET(A)) antagonism on histological and functional recovery in cat at 24 hours after reversible middle cerebral artery occlusion (MCAO). A novel and specific ET(A) antagonist, Ro 61-1790 [5-methylpyridine-2-sulfonic acid-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-1H-tetrazol-5-y l-pyridin-4-yl)-pyrimidin-4-ylamide sodium salt (1:2)] (Roche, Basel, Switzerland), was used at doses that produced steady-state plasma concentrations and abolished ET-induced pial arteriolar vasoconstriction. In a cranial window preparation, 8 nmol/L ET constricted pial arterioles by 33 +/- 18% (mean +/- SD), but this response was ablated by intravenous Ro 61-1790 treatment (10-mg/kg bolus, 4-mg/kg/h infusion). In additional animal cohorts, halothane-anesthetized cats were treated with 90 minutes of MCAO and 24 hours of reperfusion. Animals received Ro 61-1790 infusion beginning at the onset of reperfusion and continuing for 6 or 24 hours (n = 41). Control cats were treated with 0.9% saline by intravenous infusion throughout reperfusion. There was no difference in injury volume or neurologic evaluation score in saline-treated cats (n = 11; caudate 24 +/- 28%, cortical injury 7.5 +/- 5% of ipsilateral structure; score 52 +/- 8) versus the results in cats treated with Ro 61-1790 for either 24 hours (n = 6; caudate 22 +/- 23%, cortex 6 +/- 5%, injury volume of ipsilateral structure; score 55 +/- 3) or 6 hours (n = 11; caudate 33 +/- 30%, cortex 12 +/- 14%, injury volume of ipsilateral structure; score 50 +/- 10). Mortality was greatest in the 24-hour drug treatment group. These data suggest that blockade of ET(A) receptor activity is not beneficial to tissue or functional outcomes from experimental stroke in cat.

MR Imaging of Experimental Focal Cerebral Ischemia in Cats: Temporal Evolution of Hyperacute Stroke

Purpose : To evaluate the temporal evolution of the ischemic area and trace ratio, and to define ischemic penumbra within the hyperacute experimental focal cerebral ischemia model. Materials and Methods : A focal cerebral ischemia model of middle cerebral artery occlusion (MCAO) was con-structed in twelve Korean cats weighing 2-3 Kg. T2-weighted images (T2WI) and diffusion-weighted images(DWI) were obtained using a 1.5T MR imager. Trace images were reconstructed after post-image processing with IDL 5.0. The trace ratio (ipsilateral trace value/contralateral trace value) was calculated in the ischemic core and periphery, and MR images were obtained at 1, 3, 6, and 24 hrs after MCAO. The twelve cats were di-vided into three groups, and 4, 5, and 3 cats were sacrified after obtaining MR images at 3, 6, and 24 hrs after MCAO, respectively. After 2% triphenyl tetrazolium chloride (TTC) solution and formalin preparation, the in-farction area of the brain slice and T2WI and DWI trace images of the same slice were compared. The trace ratio was calculated at the peripheral portion of the ischemic core, which was the presumed ischemic penumbra in images obtained 1hr after MCAO. Changes in trace ratio in the ischemic core and infarction territory were also evaluated according to time. Results : The trace ratio in the peripheral portion of the ischemic core was 0.710.03. The region where the trace ratio was 0.830.06 in images obtained 1 hour after MCAO was presumed to be ischemic penumbra; the region progressed to infarction in images taken during the next time period. In all cases the abnormal area of trace images was larger than that seen on DWI. The trace ratio was lower, by 6.2 %, 3-6hrs after MCAO than at any other time. In cat number 3, the trace radio decreased rapidly and progressively, by 21%, during the first six hours. For 3-6hrs after MCAO, the area of infarction showed progressive enlargement. Conclusion : Within six hours of MCAO, ischemic penumbra is progressively incorporated into the ischemic core. In the experimental focal cerebral ischemia model, an area of trace ratio larger than 0.71 and less than 1may be defined as ischemic penumbra.

Endothelin-B receptors in cerebral resistance arterioles and their functional significance after focal cerebral ischemia in cats.

In the cerebral circulation, endothelin-A receptor activation mediates marked prolonged vasoconstriction whereas endothelin-B (ETB) receptor activation effects dilation. In contrast to some peripheral vascular beds, ET(B) receptor-induced vasoconstriction has not yet been demonstrated in brain vessels. In this study in chloralose-anesthetized cats, with perivascular microapplications of ET(B) selective agonist (BQ-3020) and antagonist (BQ-788), we investigated whether ET(B) receptor-mediated constriction could be uncovered in cortical arterioles in vivo. In addition, we examined whether normal dilator response to ET(B) receptor activation is preserved in postischemic cerebral arterioles. The first microapplication of the selective ET(B) receptor agonist BQ-3020 (1 micromol/L) onto a pial cortical arteriole elicited marked dilation (caliber increased by 26.3 +/- 15.1% from preinjection baseline). A second application of BQ-3020 (10-minute interval) onto the same vessel failed to evoke any significant vasomotor response. Subsequent (third and fourth) adventitial microapplication of the ET(B) receptor agonist on the same arteriolar site effected a significant constriction of cerebral arterioles (-15.3 +/- 12.7% and -9.7 +/- 6.3% from preinjection baseline, respectively, at 20 and 30 minutes after the first application). The pial arterioles did not display tachyphylaxis to repeated applications of potassium (10 mmol/L). The perivascular application of the ET(B) receptor antagonist BQ-788 (0.001 to 1 micromol/L) had no effect on arteriolar caliber per se but blocked both BQ-3020-induced dilation (inhibitory concentration approximately 5 nmol/L) and vasoconstriction elicited by repeated activation of ET(B) receptors. After middle cerebral artery occlusion, most of the arterioles examined displayed a sustained dilation. The microapplication of BQ-3020 into the perivascular space surrounding postischemic dilated arterioles elicited a constriction of a similar magnitude to that induced by application of CSF (-17 +/- 7% and -17 +/- 7% from preinjection baseline, respectively). The adventitial microapplication of the ET(B) receptor antagonist (BQ-788, 0.1 micromol/L) on postocclusion dilated pial arterioles effected no change in the arteriolar caliber when compared with preinjection baseline. This BQ-788-induced response was significantly different from that induced by perivascular microinjection of CSF (P < 0.001, analysis of variance). These investigations indicate that (1) repeated activation of ET(B) receptors displays tachyphylaxis of the vasodilator response but also uncovers significant constriction of cerebral arterioles in vivo; (2) the ability of BQ-3020 to elicit dilation is lost within 30 minutes of induced focal ischemia; and (3) ET(B)-mediated contractile tone contributes in a small but significant manner in limiting postischemia dilation of cortical pial arterioles.

Delayed hyperglycemia and intracellular acidosis during focal cerebral ischemia in cats.

The effects of hyperglycemia on permanent focal brain ischemia is controversial; its effects on the size of the infarct are variable according to experimental conditions. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to assess brain pH and high-energy phosphate metabolites after focal middle cerebral artery (MCA) ischemia in hyperglycemic and normoglycemic cats. Sixteen adult cats underwent (MCA) occlusion under general anesthesia and nuclear magnetic resonance 31P spectroscopy to assess intracellular brain pH and energy metabolites throughout permanent ischemia. Animals were treated two hours after the onset of ischemia with either saline or glucose perfusions. Significant hyperglycemia (488 vs 105 mg/100 ml) was achieved in the experimental group. The response to hyperglycemia was dependent on the initial characteristics of the infants. A distinct pattern of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia predicted a small infarct size. The addition of hyperglycemia did not affect acidosis, infarct size, or metabolite ratios in these animals. The lack of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia was predictive of an eventual large infarct. In these animals, the delayed addition of hyperglycemia significantly lowered intracellular pH during the ischemic period (5.45 vs. 6.25, p = 0.25). These data support the theory that the response to hyperglycemia is very dependent on the initial metabolic state of the injured brain. This state can be predicted by early 31P spectroscopy data, which may, in turn, prove to be a useful marker for recoverable ischemic deficit in the cerebral region of interest.

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.

We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n = 10) over 30 minutes before ischemia. Posttreatment groups received intravenous L-NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg) over the same period followed by continuous L-arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n = 10). Microsphere-determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and during ischemia, the saline-treated group, and the group treated with L-NAME plus L-arginine, respectively). Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by L-arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury.

Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats.

We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. 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 tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n = 9) or conclusion (n = 9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n = 7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15% of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25 +/- 6% [mean +/- SE]; posttreatment, 33 +/- 5%; control, 28 +/- 8% of hemisphere) or caudate nucleus (pretreatment, 46 +/- 7%; posttreatment, 41 +/- 10%; control, 55 +/- 13% of hemisphere). In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.

P-68 - Involvement of the AMPA/kainate receptor in neuronal damage induced by focal cerebral ischemia in cats : protective effects of YM90K.

P-68 - Involvement of the AMPA/kainate receptor in neuronal damage induced by focal cerebral ischemia in cats : protective effects of YM90K.

Correlation between somatosensory-evoked potentials and magnetic resonance imaging of focal cerebral ischemia in cats

Serial measurements of somatosensory-evoked potentials (SEPs) and magnetic resonance imaging (MRI) were performed in 17 cats for 24 h after unilateral middle cerebral artery occlusion. Intravoxel incoherent motion (IVIM) imaging demonstrated ischemic cerebral injury 2 h postocclusion in all cats, while T2-weighted imaging failed to show clear evidence of injury until 2–6 h. In the severely affected group of eight cats as determined by SEP criteria, ischemic injury evaluated by MR imaging was detected extensively in not only the basal ganglia but also the frontoparietal cortex including part of the somatosensory center. In contrast, in the mildly affected group of nine other cats, ischemic injury was limited to the basal ganglia with or without some involvement of the lower temporal cortex. The quantitative signal intensity ratios in the frontoparietal cortex were significantly greater in the severely affected group than in the mildly affected group, but showed no difference between them in the basal ganglia.

Effects of nilvadipine on neuronal function in the ischemic cat brain

The effect of nilvadipine, a dihydropyridine-type calcium entry blocker, on neuronal function during and following ischemia was investigated with a model of focal cerebral ischemia in cats and was compared with that of nicardipine. Drugs were given intravenously 30 minutes before occlusion of the left middle cerebral artery (MCA). Occlusion of the left MCA for 60 minutes was followed by reperfusion for 90 minutes. The amplitude of the somatosensory evoked potentials (SEPs), and the residual relative regional cortical blood flow in the left ectosylvian gyrus and the left posterior sigmoid gyrus, were higher or had a tendency toward higher values in the nilvadipine-treated (32 μg/kg) group than in other groups. After reperfusion, the amplitude of SEPs rapidly recovered in the nilvadipine-treated groups. When administered before MCA occlusion, nilvadipine improved neuronal function measured by SEPs both during and following the ischemic period. Thus, nilvadipine is effective against neuronal dysfunction in focal cerebral ischemia.

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

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. 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. 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). Inhibition of leukocyte function with MoAb 60.3 does not afford protection from severe focal ischemia and reperfusion in cats.

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)

Mri quantitation of edema in focal cerebral ischemia in cats: correlation with cytochrome aa3 oxidation state

1H MRI permits detection of edema in the brain. In a middle cerebral artery stroke model in the cat, we found a significant correlation between an edema index based on MRI and a sensitive metabolic index of ischemia, the in vivo oxidation status of mitochondrial cytochrome aa3 determined by near-infrared reflectance spectrophotometry (r = -0.70, alpha = 0.001). This result suggests that a simple, noninvasive study using MRI can provide an index of the extent of ischemic damage in an experimental acute stroke model.

Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

Selective platelet deposition during focal cerebral ischemia in cats.

Platelet deposition in the microcirculation may play a role in focal cerebral ischemia. We investigated platelet deposition in selected parts of the cat brain after temporary middle cerebral artery occlusion. Ten anesthesized cats were given autologous indium-111-labeled platelets and chromium-51-labeled erythrocytes. The right middle cerebral artery was occluded with miniature aneurysm clips for 3 hours via a transorbital approach; blood pressure was reduced concomitantly to decrease the collateral circulation. Removal of the clips initiated a 45-minute period of normotensive reperfusion. After sacrifice, the brain was removed and sectioned for comparison of right- versus left-hemisphere platelet deposition. Platelets were selectively deposited in the territory of the occluded right middle cerebral artery. Significant deposition was found in the caudate nucleus, internal capsule, parietal cortex, and the centrum semiovale. Our findings support the evidence that platelets are deposited in the microvasculature during temporary severe focal cerebral ischemia.

Effects of a new Ca 2+ antagonist, KB-2796, on the regional cerebral blood flow and somatosensory evoked potentials in the ischemic brain in cats

Effects of a new Ca 2+ antagonist, 1-[bis(4-fluorophenyl) methyl]-4-(2,3,4-trimethoxybenzyl) piperazine dihydro-chloride (KB-2796), on the regional cerebral blood flow (rCBF) and somatosensory evoked potentials (SEPs) were investigated using a model of focal cerebral ischemia in cats. In experiment 1, an occlusion of the middle cerebral artery for 4 hours persistently reduced the ipsilateral rCBF in both the control and the KB-2796-treated groups. However, the flow reduction was much milder in the treatment group than in the control group. Amplitudes of the SEPs diminished in both groups but the rate of deterioration was much slower in the treatment group than in the control group. In experiment 2, an occlusion of the middle cerebral artery for 1 hour was followed by reperfusion for 3 hours. The ipsilateral rCBF decreased during occlusion in both the control and the treatment groups. In the control group, postischemic hyperper-fusion was seen in the ectosylvian gyrus after reperfusion, whereas the ipsilateral rCBF recovered rapidly to the control values without showing a phase of hyperperfusion in the treatment group. The rate of recovery of the SEPs was also much more rapid in the treatment group.

Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology.

The spatial correlation of nuclear magnetic resonance imaging (NMRI) and cerebral blood flow (CBF) may improve our ability to identify ischemic brain lesions and may provide further insight into the pathophysiology of early cerebral ischemia. Eleven pentobarbital-anesthetized adult cats underwent exposure of the common carotid arteries bilaterally and the right middle cerebral artery through a transorbital approach. Baseline NMRI images were obtained with a single spin-echo, multislice technique using a 0.6-T field, 0.4-cm slice thickness, and a surface coil. Focal ischemia was produced with right middle cerebral artery occlusion and potentiated with bilateral common carotid artery ligation. Sequential NMRI studies were then performed at 1, 2, 4, 6, and 12 hours or until CBF was determined in the same cats using [14C]iodoantipyrine at either 2 (n = 2), 4 (n = 2), 6 (n = 2), or 12 (n = 1) hours after the time of occlusion. This protocol allowed temporal and spatial correlation of NMRI and CBF. Alternate 5-mm brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride (TTC) for 45 minutes at 37-41 degrees C and frozen in liquid Freon for later autoradiographic CBF determination. Four cats were studied only with NMRI and TTC (not CBF). The correlation between areas of increased NMRI signal intensity observed in T2-weighted images (repetition time 2,000 msec, echo time 120 msec), vital staining with TTC, low CBF, and routine histology was evaluated. During the early phase (less than 6 hours), T2-weighted NMRI changes were localized to the central ischemic gray matter areas, as defined in the later CBF images, with no involvement of the white matter. By the twelfth hour the NMRI changes involved the entire ischemic area including gray and white matter. The initial visible changes seen on T2-weighted NMRI are suggestive of cellular edema, and the later changes are characteristic of vasogenic edema. The spread of NMRI changes compared with the ischemic area determined from autoradiographic CBF is consistent with the previously described biphasic evolution of ischemic injury. These data suggest that T2-weighted NMRI could be used clinically to delineate areas of acute ischemic stroke.

The Protective Effect of Mannitol and Methylprednisolone in the Acute Focal Cerebral Ischemia in Cats

The Protective Effect of Mannitol and Methylprednisolone in the Acute Focal Cerebral Ischemia in Cats

Extracellular K+, microflow and NAD/NADH changes in focal cerebral ischemia in cats.

The interrelationship of electrical function of the brain, the extra-cellular K+, NADH fluorescence and microflow was studied in acute focal cerebral ischemia in cats. The electrical activity, extracellular potassium (K+ e) changes and fluororeflectometry (NAD/NADH redox state and microflow) were measured in the middle ectosylvian gyrus in closed skull animals. The middle cerebral artery was clamped for two hours, and the observation was followed four additional hours after the release of the occlusion. The animals were classified into three distinct groups based on electrophysiological criteria. The severe stroked animals showed more than 80% reduction in the ratio of the electrical activity of the occluded territory to that on the contralateral side. In the moderate group the ECoG ratio was between 0.2–0.7 and if the ratio was over 0.7, the animals were classified as mild.