Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage

Haiying Lu,1,* Mei Jiang,2,* Lei Lu,3 Guo Zheng,1 Qiang Dong3 1Department of Neurology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, 2Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 3Department of Neurology, Huashan Hospital, Fudan Univers...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Lu H, Jiang M, Lu L, Zheng G, Dong Q
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://doaj.org/article/536149a25fd84b6cbf0f9de42b6e68ff
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:536149a25fd84b6cbf0f9de42b6e68ff
record_format dspace
spelling oai:doaj.org-article:536149a25fd84b6cbf0f9de42b6e68ff2021-12-02T03:53:38ZUltrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage1178-2021https://doaj.org/article/536149a25fd84b6cbf0f9de42b6e68ff2015-10-01T00:00:00Zhttps://www.dovepress.com/ultrastructural-mitochondria-changes-in-perihematomal-brain-and-neurop-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Haiying Lu,1,* Mei Jiang,2,* Lei Lu,3 Guo Zheng,1 Qiang Dong3 1Department of Neurology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, 2Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 3Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Aim: The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods: Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results: Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion: These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. Keywords: apoptosis, intracerebral hemorrhage, mitochondria, huperzine A, neuroprotectionLu HJiang MLu LZheng GDong QDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2015, Iss default, Pp 2649-2657 (2015)
institution DOAJ
collection DOAJ
language EN
topic Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Lu H
Jiang M
Lu L
Zheng G
Dong Q
Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
description Haiying Lu,1,* Mei Jiang,2,* Lei Lu,3 Guo Zheng,1 Qiang Dong3 1Department of Neurology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, 2Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 3Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Aim: The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods: Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results: Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion: These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. Keywords: apoptosis, intracerebral hemorrhage, mitochondria, huperzine A, neuroprotection
format article
author Lu H
Jiang M
Lu L
Zheng G
Dong Q
author_facet Lu H
Jiang M
Lu L
Zheng G
Dong Q
author_sort Lu H
title Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
title_short Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
title_full Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
title_fullStr Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
title_full_unstemmed Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage
title_sort ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of huperzine a after acute intracerebral hemorrhage
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/536149a25fd84b6cbf0f9de42b6e68ff
work_keys_str_mv AT luh ultrastructuralmitochondriachangesinperihematomalbrainandneuroprotectiveeffectsofhuperzineaafteracuteintracerebralhemorrhage
AT jiangm ultrastructuralmitochondriachangesinperihematomalbrainandneuroprotectiveeffectsofhuperzineaafteracuteintracerebralhemorrhage
AT lul ultrastructuralmitochondriachangesinperihematomalbrainandneuroprotectiveeffectsofhuperzineaafteracuteintracerebralhemorrhage
AT zhengg ultrastructuralmitochondriachangesinperihematomalbrainandneuroprotectiveeffectsofhuperzineaafteracuteintracerebralhemorrhage
AT dongq ultrastructuralmitochondriachangesinperihematomalbrainandneuroprotectiveeffectsofhuperzineaafteracuteintracerebralhemorrhage
_version_ 1718401548160073728