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

<h4>Background and purpose</h4>To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).<h4>Methods</h4>70 male Wistar rats were categorized i...

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Autores principales: 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
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:f7a63de9084141b09ad1a8690d99bbde2021-11-18T08:14:16ZLocal delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.1932-620310.1371/journal.pone.0042597https://doaj.org/article/f7a63de9084141b09ad1a8690d99bbde2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049732/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and purpose</h4>To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Daniel HänggiJason PerrinSven EickerKerim BeseogluNima EtminanMarcel Alexander KampHi-Jae HeirothNadia BegeStephan MachtKatrin FrauenknechtClemens SommerThomas KisselHans-Jakob SteigerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e42597 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
description <h4>Background and purpose</h4>To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format article
author 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
author_facet 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
author_sort Daniel Hänggi
title Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
title_short Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
title_full Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
title_fullStr Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
title_full_unstemmed Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
title_sort local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f7a63de9084141b09ad1a8690d99bbde
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