Journal Article

Local Delivery of Nimodipine by Prolonged-Release Microparticles—Feasibility, Effectiveness and Dose-Finding in Experimental Subarachnoid Hemorrhage

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

2012

Overview

To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH). 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Angiography / Angiography, Digital Subtraction / Animals / Biology / Brain / Brain - blood supply / Brain - diagnostic imaging / Brain - drug effects / Brain - pathology / Brain injuries / Brain injury / Calcium-Binding Proteins - genetics / Complications and side effects / Delayed-Action Preparations - administration & dosage / Delayed-Action Preparations - chemistry / Dimensional analysis / Dosage and administration / Dose-Response Relationship, Drug / Drug Administration Schedule / Drug therapy / Feasibility studies / Gene Expression - drug effects / Genetic aspects / Head injuries / Hemorrhage / Immunohistochemistry / Injections, Intravenous / Kinases / Laboratory animals / Lactic Acid - administration & dosage / Lactic Acid - chemistry / Male / Medical imaging / Medicine / Microfilament Proteins - genetics / Microparticles / Microtubule-Associated Proteins - genetics / Neuropathology / Neurosurgery / Nimodipine / Nimodipine - pharmacology / Nimodipine - therapeutic use / Pharmaceutical sciences / Polyglycolic Acid - administration & dosage / Polyglycolic Acid - chemistry / Polylactic Acid-Polyglycolic Acid Copolymer / Proteins / Rats / Rats, Wistar / Stroke / Studies / Subarachnoid hemorrhage / Subarachnoid Hemorrhage - diagnostic imaging / Subarachnoid Hemorrhage - drug therapy / Subarachnoid Hemorrhage - pathology / Toxicity / Vasoconstriction / Vasodilator Agents - pharmacology / Vasodilator Agents - therapeutic use / Vasospasm, Intracranial - diagnostic imaging / Vasospasm, Intracranial - drug therapy / Vasospasm, Intracranial - pathology