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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiography, Digital Subtraction
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Animals
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Brain / blood supply
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Brain / diagnostic imaging
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Brain / drug effects*
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Brain / pathology
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Calcium-Binding Proteins / genetics
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Delayed-Action Preparations / administration & dosage*
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Delayed-Action Preparations / chemistry
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Gene Expression / drug effects
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Immunohistochemistry
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Injections, Intravenous
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Lactic Acid / administration & dosage*
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Lactic Acid / chemistry
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Male
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Microfilament Proteins / genetics
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Microtubule-Associated Proteins / genetics
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Nimodipine / pharmacology
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Nimodipine / therapeutic use*
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Polyglycolic Acid / administration & dosage*
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Polyglycolic Acid / chemistry
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Polylactic Acid-Polyglycolic Acid Copolymer
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Rats
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Rats, Wistar
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Subarachnoid Hemorrhage / diagnostic imaging
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Subarachnoid Hemorrhage / drug therapy*
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Subarachnoid Hemorrhage / pathology
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Vasodilator Agents / pharmacology
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Vasodilator Agents / therapeutic use*
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Vasospasm, Intracranial / diagnostic imaging
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Vasospasm, Intracranial / drug therapy*
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Vasospasm, Intracranial / pathology
Substances
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Aif1 protein, rat
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Calcium-Binding Proteins
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Delayed-Action Preparations
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MAP2 protein, rat
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Microfilament Proteins
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Microtubule-Associated Proteins
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Vasodilator Agents
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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Nimodipine
Grants and funding
The study was supported by a grant of the Klüh Foundation, Düsseldorf, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.