Ruiming Shen1, Jian Zhou2, Ge Li3, Wuyan Chen4, Wangwang Zhong5, Zhenggang Chen5. 1. Department of Rheumatology, The First Affiliated Hospital of Hainan Medical University, 31 Longhua Road, Haikou, 570102, Hainan Province, China. 2. Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University,31 Longhua Road, Haikou, 570102, Hainan Province, China. Electronic address: hkjianzhou@hotmail.com. 3. The Second Ward, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, 31 Longhua Road, Haikou, 570102, Hainan Province, China. 4. The First Ward, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, 31 Longhua Road, Haikou, 570102, Hainan Province, China. 5. Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University,31 Longhua Road, Haikou, 570102, Hainan Province, China.
Abstract
BACKGROUND: SS31 has been shown to have neuroprotective effects in a number of neurological degenerative diseases. However, the mechanisms and its role of neuroprotection after subarachnoid hemorrhage (SAH) remain unexplored. The aim of the present study is to evaluate the neuroprotective effects of SS31 on early brain injury (EBI) induced by SAH in rats and the potential mechanisms of the protective effects of SS31. METHODS: Sprague-Dawley rats were randomly divided into four groups: Sham, SAH, SAH + vehicle, and SAH + SS31 groups. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological scores were evaluated at 24 h and 72 h after SAH. The brain edema, blood-brain barrier (BBB) permeability, neuronal apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, as well as the expression of mitochondrial and cytosolic cytochrome C (Cyt C), and Bax were analyzed at 24 h after SAH. RESULTS: When compared with the vehicle-treated group, treatment with SS31 significantly reduced MDA levels and restored the activities of GPx and SOD in the temporal cortex following SAH when compared with the vehicle-treated group. In addition, the levels of mitochondrial Cyt C and Bax respectively increased and decreased by SS31 treatment. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH. CONCLUSION: Our data provides initial evidence that SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibiting neuronal apoptosis, likely by modulating the mitochondrial apoptotic pathway.
BACKGROUND: SS31 has been shown to have neuroprotective effects in a number of neurological degenerative diseases. However, the mechanisms and its role of neuroprotection after subarachnoid hemorrhage (SAH) remain unexplored. The aim of the present study is to evaluate the neuroprotective effects of SS31 on early brain injury (EBI) induced by SAH in rats and the potential mechanisms of the protective effects of SS31. METHODS:Sprague-Dawley rats were randomly divided into four groups: Sham, SAH, SAH + vehicle, and SAH + SS31 groups. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological scores were evaluated at 24 h and 72 h after SAH. The brain edema, blood-brain barrier (BBB) permeability, neuronal apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, as well as the expression of mitochondrial and cytosolic cytochrome C (Cyt C), and Bax were analyzed at 24 h after SAH. RESULTS: When compared with the vehicle-treated group, treatment with SS31 significantly reduced MDA levels and restored the activities of GPx and SOD in the temporal cortex following SAH when compared with the vehicle-treated group. In addition, the levels of mitochondrial Cyt C and Bax respectively increased and decreased by SS31 treatment. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH. CONCLUSION: Our data provides initial evidence that SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibiting neuronal apoptosis, likely by modulating the mitochondrial apoptotic pathway.