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Neurological Disorders - Pharmacology - Surgery


Local Delivery of Nimodipine by Prolonged-Release Microparticles—Feasibility, Effectiveness and Dose-Finding in Experimental Subarachnoid Hemorrhage
Published: Tuesday, September 25, 2012
Author: Daniel Hänggi et al.

by Daniel Hänggi, Jason Perrin, Sven Eicker, Kerim Beseoglu, Nima Etminan, Marcel Alexander Kamp, Hi-Jae Heiroth, Nadia Bege, Stephan Macht, Katrin Frauenknecht, Clemens Sommer, Thomas Kissel, Hans-Jakob Steiger

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.

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