Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway.
This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH.
Department of Neurosurgery, School of Medicine, Southern Medical University, Jinling Hospital, 305 East Zhongshan Road, Nanjing, Jiangsu Province 210002, China; Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
Shaoxue
0000-0002-1404-902X
S
Li
Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
Xiaolan
X
Xiao
Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
Xiaojia
0000-0001-6624-5244
X
Ni
Department of Neurosurgery, School of Medicine, Southern Medical University, Jinling Hospital, 305 East Zhongshan Road, Nanjing, Jiangsu Province 210002, China.
Zhennan
0000-0001-6040-5075
Z
Ye
Surgery & Interventional Science, Royal Free Hospital, University College London Medical School, Pond Street, London, UK.
Junjie
0000-0002-3696-8991
J
Zhao
Department of Neurosurgery, School of Medicine, Southern Medical University, Jinling Hospital, 305 East Zhongshan Road, Nanjing, Jiangsu Province 210002, China.
Chunhua
0000-0001-8687-7599
C
Hang