Dose-related efficacy of a continuous intracisternal nimodipine treatment on cerebral vasospasm in the rat double subarachnoid hemorrhage model
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Dose-related efficacy of a continuous intracisternal nimodipine treatment on cerebral vasospasm in the rat double subarachnoid hemorrhage model. / Hänggi, Daniel; Eicker, Sven; Beseoglu, Kerim; Rapp, Marion; Perrin, Jason; Nawatny, Jens; Turowski, Bernd; Sommer, Clemens; Steiger, Hans-Jakob.
In: NEUROSURGERY, Vol. 64, No. 6, 06.2009, p. 1155-9; discussion 1159-61.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Dose-related efficacy of a continuous intracisternal nimodipine treatment on cerebral vasospasm in the rat double subarachnoid hemorrhage model
AU - Hänggi, Daniel
AU - Eicker, Sven
AU - Beseoglu, Kerim
AU - Rapp, Marion
AU - Perrin, Jason
AU - Nawatny, Jens
AU - Turowski, Bernd
AU - Sommer, Clemens
AU - Steiger, Hans-Jakob
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Animals
KW - Antihypertensive Agents
KW - Cerebral Angiography
KW - Dose-Response Relationship, Drug
KW - Drug Contamination
KW - Male
KW - Nimodipine
KW - Random Allocation
KW - Rats
KW - Rats, Wistar
KW - Subarachnoid Hemorrhage
KW - Vasospasm, Intracranial
U2 - 10.1227/01.NEU.0000340685.06407.FD
DO - 10.1227/01.NEU.0000340685.06407.FD
M3 - SCORING: Journal article
C2 - 19487896
VL - 64
SP - 1155-9; discussion 1159-61
JO - NEUROSURGERY
JF - NEUROSURGERY
SN - 0148-396X
IS - 6
ER -
