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


CONCLUSIONS
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.
Department of Neurology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Haiying
H
Lu
Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Mei
M
Jiang
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Lei
L
Lu
Department of Neurology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Guo
G
Zheng
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Qiang
Q
Dong
apoptosis; huperzine A; intracerebral hemorrhage; mitochondria; neuroprotection