Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage
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Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage. / Hänggi, Daniel; Perrin, Jason; Eicker, Sven; Beseoglu, Kerim; Etminan, Nima; Kamp, Marcel Alexander; Heiroth, Hi-Jae; Bege, Nadia; Macht, Stephan; Frauenknecht, Katrin; Sommer, Clemens; Kissel, Thomas; Steiger, Hans-Jakob.
In: PLOS ONE, Vol. 7, No. 9, 2012, p. e42597.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage
AU - Hänggi, Daniel
AU - Perrin, Jason
AU - Eicker, Sven
AU - Beseoglu, Kerim
AU - Etminan, Nima
AU - Kamp, Marcel Alexander
AU - Heiroth, Hi-Jae
AU - Bege, Nadia
AU - Macht, Stephan
AU - Frauenknecht, Katrin
AU - Sommer, Clemens
AU - Kissel, Thomas
AU - Steiger, Hans-Jakob
PY - 2012
Y1 - 2012
N2 - BACKGROUND AND PURPOSE: To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).METHODS: 70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry.RESULTS: DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury.CONCLUSIONS: Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.
AB - BACKGROUND AND PURPOSE: To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).METHODS: 70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry.RESULTS: DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury.CONCLUSIONS: Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.
KW - Angiography, Digital Subtraction
KW - Animals
KW - Brain
KW - Calcium-Binding Proteins
KW - Delayed-Action Preparations
KW - Dose-Response Relationship, Drug
KW - Drug Administration Schedule
KW - Gene Expression
KW - Immunohistochemistry
KW - Injections, Intravenous
KW - Lactic Acid
KW - Male
KW - Microfilament Proteins
KW - Microtubule-Associated Proteins
KW - Nimodipine
KW - Polyglycolic Acid
KW - Rats
KW - Rats, Wistar
KW - Subarachnoid Hemorrhage
KW - Vasodilator Agents
KW - Vasospasm, Intracranial
U2 - 10.1371/journal.pone.0042597
DO - 10.1371/journal.pone.0042597
M3 - SCORING: Journal article
C2 - 23049732
VL - 7
SP - e42597
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 9
ER -
