Acute Improvement in Histological Outcome by MK-801 following Focal Cerebral Ischemia and Reperfusion in the Cat Independent of Blood Flow Changes

The present study reports on the acute effects of MK-801 on the histopathological outcome and blood flow changes during focal cerebral ischemia and reperfusion. In addition, acute changes in the EEG and blood pressure are also reported. In 16 halothane-anesthetized cats, the left middle cerebral artery (MCA) was occluded for 2 h followed by 4 h of reperfusion. Thirty minutes after the onset of ischemia, eight animals were treated with 1 mg/kg of MK-801, while eight animals received saline. Blood flow from the peripheral MCA territory was measured with H2 clearance. There was a comparable reduction in blood flow (down to 20% of control) in the ischemic gyri of the two groups followed by a partial recovery after recirculation. There was a similar decrease in the EEG amplitude over the ischemic central MCA territory in the treated and the untreated group. Treatment with MK-801 induced a burst suppression in the EEG and a transient drop (11.4 ± 6.5 mm Hg) in the mean arterial pressure. The volume of early ischemic damage decreased by one-third in the MK-801-treated group compared to the untreated one, both in the total hemisphere (from 29 ± 10 to 20 ± 5%) and in the hemispheric cortex (range 36 ± 8 to 24 ± 13%). A major fraction of this improvement was localized to the middle and posterior parietal (mainly perifocal) regions of the MCA territory. These results show that in our model, MK-801 improves histopathological outcome despite the lack of apparent effect on the cortical blood flow, and an adverse effect on the systemic blood pressure. This is the first report that describes data on a reproducible model of reperfusion after temporary occlusion of the MCA in a cat, extending the findings of the Glasgow group, who observed similar neuroprotection in models of permanent MCA occlusion.

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Effects of Normobaric Hyperoxia in a Rat Model of Transient Focal Cerebral Ischemia and Reperfusion

Stroke ◽

10.1161/str.32.suppl_1.316-b ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 316-316

Author(s):

Aneesh B Singhal ◽

Xiaoying Wang ◽

Eng H Lo

Keyword(s):

Blood Flow ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Blue Dye ◽

Ischemia And Reperfusion ◽

Normobaric Hyperoxia ◽

Doppler Flowmetry ◽

Normobaric Oxygen ◽

Cerebral Ischemia And Reperfusion

3 Background: The role of therapeutic oxygen in treatment of acute stroke is controversial. Oxygen improves cellular aerobic metabolism and can salvage ischemic tissue. However, oxygen free radicals can increase blood brain barrier (BBB) damage, and oxygen can induce vasoconstriction, which could worsen stroke outcome. We studied the effects of normobaric oxygen in cerebral ischemia and reperfusion. Methods: Rats were subjected to normobaric hyperoxia (FiO2 100%) or normoxia (FiO2 30%) during two hour filament occlusion and one hour reperfusion of the middle cerebral artery. Twenty-four hour infarct volumes, regional cerebral blood flow (rCBF) using laser Doppler flowmetry, and severity of BBB damage (assessed by quantifying Evan’s Blue dye (EB) leakage after one hour of reperfusion) were compared between groups. Results: Physiological parameters were similar in hyperoxic and control groups, except for paO2, which was expectedly higher in the hyperoxic group (pO2 484 mm Hg) as compared to controls (pO2 118 mm Hg). Mean rCBF dropped to 25% after onset of ischemia and recovered to 75–90% after arterial unocclusion, indicating successful reperfusion. Mean total (right hemispheric) infarct volume was 65 mm 3 in the hyperoxia group and 209 mm 3 in controls, p<0.001. The reduction in infarct volume was mostly in the cortex, where mean infarct volume was 11 mm 3 in hyperoxic rats and 129 mm 3 in controls (p<0.001). Mean striatal infarct volume was 54 mm 3 in hyperoxic rats and 80 mm 3 in controls (p<0.06). Mean total EB leak was 1592 ng/g in hyperoxic and 3955 ng/g in control rats (p<0.02), suggesting reduced BBB damage in hyperoxia. However, BBB damage and EB leak are likely related to infarct volume; after normalising for infarct volume, mean EB leak was 17 ng/mm3 in the hyperoxia group and 14 ng/mm3 in controls (p=0.5). Conclusion: Total and cortical infarct volumes can be significantly reduced with normobaric hyperoxia during transient cerebral ischemia and reperfusion. Hyperoxia does not decrease blood flow to ischemic brain, and its benefit in reducing infarct volume may outweigh any potential damage from BBB damage.

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Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia

Journal of Neurosurgery ◽

10.3171/jns.1989.70.1.0073 ◽

1989 ◽

Vol 70 (1) ◽

pp. 73-80 ◽

Cited By ~ 41

Author(s):

Toshihiko Kuroiwa ◽

Makoto Shibutani ◽

Riki Okeda

Keyword(s):

Blood Flow ◽

Cerebral Ischemia ◽

Brain Edema ◽

Focal Cerebral Ischemia ◽

Reactive Hyperemia ◽

Diffusion Method ◽

Left Middle Cerebral Artery ◽

Content Type ◽

Bbb Opening ◽

Fine Print

✓ The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

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