Article
Dose-related efficacy of a continuous intracisternal nimodipine treatment on cerebral vasospasm in the rat double subarachnoid haemorrhage model
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Published: | May 20, 2009 |
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Objective: Intracisternal continuous therapy is a concept in the treatment of cerebral vasospasm after subarachnoid haemorrhage (SAH). The purpose of the current study was to investigate the effect of intracisternal nimodipine after induced vasospasm.
Methods: 65 male Wistar rats were randomized into four groups; the control sham operated group, the control SAH only group and the treatment groups receiving 5 µl/h or 10 µl/h intracisternal nimodipine continuously for 5 days via subcutaneously implanted ALZET® osmotic pumps. Vasospasm was analyzed 5 days later by means of digital subtraction angiography (DSA). Morphological examination of the brain parenchyma was performed using Nissl-staining, c-Fos immunohistochemistry and TUNEL staining.
Results: Detailed analysis of the DSA was possible for 31 animals. Significant angiographic vasospasm was induced with the double haemorrhage only group compared to the sham operated group (p=0.002). Between the four groups there were statistically significant differences of the arterial vessel caliber as measured by DSA (p=0.001, Kruskal-Wallis test). The treatment group receiving 5µl/h of nimodipine and the control sham operated group demonstrated the largest intracranial artery diameters with a significant difference between control SAH only group and the treatment group receiving 10µl/h of nimodipine (p=0.0328, Wilcoxon rank-sum-test). In all SAH groups, a few scattered TUNEL positive cells were detectable.
Conclusions: Intracisternal nimodipine lavage with 5µl/h, but not with 10µl/h leads to significant arterial relaxation. Further research is necessary to elucidate the underlying cause of decreasing nimodipine effect at higher dosage.