Axonal dysfunction in internal capsule is closely associated with early motor deficits after intracerebral hemorrhage in mice
| Autor: | Hayato Ishibashi, Yuki Kurauchi, Masanori Hijioka, Junpei Anan, Hideaki Matsushita, Takahiro Seki, Hiroshi Katsuki, Akinori Hisatsune |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Neurofilament Internal capsule Motor Disorders Axonal Transport Amyloid beta-Protein Precursor 03 medical and health sciences 0302 clinical medicine Thrombin Internal Capsule Thrombin receptor medicine Animals Collagenases cardiovascular diseases Cerebral Hemorrhage Intracerebral hemorrhage business.industry General Neuroscience General Medicine medicine.disease Axons Mice Inbred C57BL 030104 developmental biology nervous system Corticospinal tract Axoplasmic transport Colchicine business Neuroscience 030217 neurology & neurosurgery Immunostaining medicine.drug |
| Zdroj: | Neuroscience Research. 106:38-46 |
| ISSN: | 0168-0102 |
| DOI: | 10.1016/j.neures.2015.10.006 |
| Popis: | Previously we showed that expansion of intracerebral hemorrhage (ICH) into the internal capsule greatly aggravated neurological symptoms in mice. Here we examined ICH-associated events in the internal capsule with relation to neurological dysfunction. Corticospinal axons labeled by biotinylated dextran amine exhibited fragmented appearance after ICH induced by local injection of collagenase into the internal capsule. Fragmentation of axonal structures was confirmed by neurofilament-H immunostaining, which was evident from 6h after induction of ICH. We also observed accumulation of amyloid precursor protein, which indicated compromised axonal transport, from 3h after induction of ICH. The early defect in axonal transport was accompanied by a robust decline in motor performance. Local application of an axonal transport inhibitor colchicine to the internal capsule induced a prompt decline in motor performance, suggesting that compromised axonal transport is closely associated with early neurological dysfunction in ICH. Arrest of axonal transport and fragmentation of axonal structures were also induced by local injection of thrombin, but not by thrombin receptor activator peptide-6, a protease-activated receptor-1 agonist. These results suggest that receptor-independent actions of thrombin mediate disruption of structure and function of axons by hemorrhage expansion into the internal capsule, which leads to severe neurological dysfunction. |
| Databáze: | OpenAIRE |
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