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...
Guardado en:
Autores principales: | , , , , |
---|---|
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 |