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PLoS One. 2012;7(9):e42597. doi: 10.1371/journal.pone.0042597. Epub 2012 Sep 25.

Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.

Author information

  • 1Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany. daniel.haenggi@uni-duesseldorf.de

Abstract

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.

PMID:
23049732
[PubMed - indexed for MEDLINE]
PMCID:
PMC3458040
Free PMC Article
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