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  • Title: Dose-related efficacy of a continuous intracisternal nimodipine treatment on cerebral vasospasm in the rat double subarachnoid hemorrhage model.
    Author: Hänggi D, Eicker S, Beseoglu K, Rapp M, Perrin J, Nawatny J, Turowski B, Sommer C, Steiger HJ.
    Journal: Neurosurgery; 2009 Jun; 64(6):1155-9; discussion 1159-61. PubMed ID: 19487896.
    Abstract:
    OBJECTIVE: Intracisternal continuous therapy is a concept in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The purpose of the current study was to investigate the effect of intracisternal nimodipine after induced vasospasm. METHODS: Sixty-five male Wistar rats were randomized into 4 groups: the control sham-operated group, the control subarachnoid hemorrhage-only group, and the treatment groups receiving 5 or 10 microL/hour of intracisternal nimodipine continuously for 5 days via subcutaneously implanted Alzet osmotic pumps (Durect Corp., Cupertino, CA). Vasospasm was analyzed 5 days later by means of digital subtraction angiography. Morphological examination of the brain parenchyma was performed using Nissl-staining, c-Fos immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. RESULTS: Detailed analysis of the digital subtraction angiography was possible for 31 animals. Significant angiographic vasospasm was induced in the double hemorrhage-only group compared with the sham-operated group (P = 0.002). Among the 4 groups, there were statistically significant differences of the arterial vessel caliber as measured by digital subtraction angiography (P = 0.001, Kruskal-Wallis test). The treatment group receiving 5 microL/hour of nimodipine and the control sham-operated group demonstrated the largest intracranial artery diameters with a significant difference between control subarachnoid hemorrhage-only group and the treatment group receiving 10 microL/hour of nimodipine (P = 0.0328, Wilcoxon rank-sum test). Variation in vessel calibers, however, did not result in different brain tissue alterations, even when using sensitive markers for the induction of the stress response or apoptosis. CONCLUSION: Intracisternal nimodipine lavage with 5 microL/hour, but not with 10 microL/hour leads to significant arterial relaxation. Further research is needed to elucidate the underlying cause of the decreasing nimodipine effect at higher dosage.
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