Nimodipine and the Haemodynamic and Histopathological Consequences of Middle Cerebral Artery Occlusion in the Rat

Gotoh, Osamu; Mohamed, A. A.; McCulloch, James; Graham, David I.; Harper, A. M.; Teasdale, Graham M.

doi:10.1038/jcbfm.1986.55

Cited by 146 publications

(24 citation statements)

References 22 publications

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“…Preischemic treatment with nimodipine im proved CBF in middle cerebral artery-occluded rats (Mohamed et aI., 1985b) and tissue pH in rab bits (Tally et aI., 1989). An increase in CBF in the middle cerebral artery occlusion model of the rat was not found when nimodipine was given after in duction of ischemia (Graham et aI., 1985;Gotoh et al, 1986). Adverse results were obtained in neuro pathological quantification of the ischemic damage, too.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Nimodipine against Ischemic Neuronal Damage in Rat Hippocampus without Changing Postischemic Cerebral Blood Flow

Nuglisch

Karkoutly²,

et al. 1990

J Cereb Blood Flow Metab

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The purpose of the present study was to investigate the neuroprotective action of nimodipine. Furthermore, the influence of nimodipine on postischemic local CBF (LCBF) was examined. Forebrain ischemia of the rat was performed for 10 min by bilateral carotid clamping, administration of trimethaphan, and blood withdrawal to obtain an MABP of 40 mm Hg. LCBF was measured after 10 min of postischemic recirculation by injecting [14C]iodoantipyrine in saline solution. Nimodipine (0.1, 0.3, and 1.0 mg/kg) was suspended in miglyol oil and applied orally 60 min prior to ischemia. Histological evaluation was performed 7 days after ischemia. Hippocampal neuronal damage was determined as the percentage of necrotic neurons. After preischemic application of nimodipine, neuronal damage was significantly reduced in the hippocampal CA1 subfield. Postischemic LCBF was not affected by treatment with nimodipine. These findings show that nimodipine is able to protect neurons against ischemic damage. The neuroprotective effect of nimodipine was not mediated by a postischemic cerebral vasodilation, but by a direct action on the neurons.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Nimodipine against Ischemic Neuronal Damage in Rat Hippocampus without Changing Postischemic Cerebral Blood Flow

Nuglisch

Karkoutly²,

et al. 1990

J Cereb Blood Flow Metab

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“…16,21,[25][26][27][28][29][30][31][32][33][34] One study did not state the length of this interval. 35 The methodological quality of the included studies was poor (median 2.85 points, range 1 to 5).…”

Section: Description Of Studiesmentioning

confidence: 99%

Nimodipine in Animal Model Experiments of Focal Cerebral Ischemia

Horn

Haan

Vermeulen

et al. 2001

Stroke

197

139

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Background and Purpose-Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials. Methods-We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies. Results-Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found. Conclusions-We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.

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“…These sections were stained with hematoxylin and eosin. For morphometric study, ten coronal levels were selected at defined anatomic landmarks (Gotoh et al, 1986). Each section was viewed at low power (x 10), and the infarcted area was traced onto paper using a cam era lucida microscope attachment.…”

Section: Histopathological Evaluationmentioning

confidence: 99%

The Significance of Brain Temperature in Focal Cerebral Ischemia: Histopathological Consequences of Middle Cerebral Artery Occlusion in the Rat

Morikawa

Ginsberg

Dietrich

et al. 1992

J Cereb Blood Flow Metab

338

109

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Summary: The purpose of this study was to determine the effect of selective modulation of brain temperature in the experimental settings of permanent and reversible middle cerebral artery (MCA) occlusion in Sprague Dawley rats. Three models of proximal MCA occlusion were used, in which the effect of brain-temperature mod ulations could be studied. These included (a) permanent MCA occlusion with an initial 30-min period of hypoten sion (30 or 36°C x 4 h), (b) permanent MCA occlusion alone (30, 36, or 39°C x 2 h), and (c) 2 h of reversible MCA occlusion (30, 36, or 39°C x 2 h). In the transient MCA occlusion series, intra-and postischemic cortical blood flow was assessed using a laser-Doppler flowmeter placed over the dorsolateral cortex. After a 3-day sur vival, all rats were perfusion fixed for histopathological analysis and the determination of infarct volume. In ani mals with permanent MCA occlusion plus hypotension, no significant difference in infarct volume was demon strated between the 30 and 36°C groups. In rats with per manent MCA occlusion without hypotension, significantBeneficial effects of hypothermia have been well established in the experimental settings of brain anoxia and hypoxia-ischemia (Michenfelder and Theye, 1970; Berntman et aI., 1981 ; Young et aI., 1983) and in temporary complete global cerebral ischemia (Connolly et al., 1962; Marshall et aI., 1956; Kramer et aI., 1968; Kopf et aI., 1975). Recent 380differences in infarct volume were again not demonstra ble, but an interaction between infarct area and temper ature class was shown by repeated-measures analysis, indicating that hypothermia altered the topographic pat tern of the cortical infarct. With 2 h of reversible MCA occlusion, there was a statistically significant reduction in infarct volume in the 30°C groJlP compared to 39°C rats. Although intra-and postischemic CBP were not signifi cantly different among the three temperature groups, the cortical infarct volume was positively correlated with postischemic CBP. The postischemic CBP, in turn, was positively correlated to the intraischemic brain tempera ture and was negatively correlated to CBP during the ischemic period. These findings demonstrate that moder ate manipUlations of brain temperature have a greater in fluence on the resulting cortical infarction in the setting of transient focal ischemia than in the context of permanent vascular occlusion.

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Nimodipine and the Haemodynamic and Histopathological Consequences of Middle Cerebral Artery Occlusion in the Rat

Cited by 146 publications

References 22 publications

Protective Effect of Nimodipine against Ischemic Neuronal Damage in Rat Hippocampus without Changing Postischemic Cerebral Blood Flow

Protective Effect of Nimodipine against Ischemic Neuronal Damage in Rat Hippocampus without Changing Postischemic Cerebral Blood Flow

Nimodipine in Animal Model Experiments of Focal Cerebral Ischemia

The Significance of Brain Temperature in Focal Cerebral Ischemia: Histopathological Consequences of Middle Cerebral Artery Occlusion in the Rat

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