Xiaoyan Shen1,2, Guiqiang Yuan1, Bing Li1,3, Cheng Cao1,4, Demao Cao1,5, Jiang Wu1, Xiang Li1, Haiying Li1, Haitao Shen6, Zhong Wang7, Gang Chen1. 1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. 2. Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, China. 3. Department of Neurosurgery, Yancheng City No. 1 People's Hospital, The Fourth Affiliated Hospital of Nantong University, Yancheng, Jiangsu Province, China. 4. Department of Neurocritical Intensive Care Unit, The Affiliated Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu Province, China. 5. Department of Neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China. 6. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. shenhaitao1990@suda.edu.cn. 7. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. wangzhong8761@163.com.
Abstract
BACKGROUND: Early brain injury (EBI) has been considered as the major contributor to the neurological dysfunction and poor clinical outcomes of subarachnoid hemorrhage (SAH). Studies showed that apelin-13 exhibits a neuroprotective effect in brain damage induced by cerebral ischemia. However, it remains unclear whether apelin-13 could exhibit the protective functions following SAH. The present study aimed to validate the neuroprotective role of apelin-13 in SAH, and further investigated the underlying mechanisms. METHODS AND RESULTS: We constructed SAH rat model and we found that apelin-13 significantly alleviated neurological disorder and brain edema, improved memory deficits in SAH rats. Apelin-13 treatment decreased contents of TNF-α and IL-1β in cerebral spinal fluid of SAH rat by using ELISA. Apelin-13 treatment promoted the expression of APJ and Bcl-2, and decreased the level of active caspase-3 and Bax in the temporal cortex after SAH by using western blot. Also, apelin-13 attenuated the cortical cell death and neuronal degeneration as shown by TUNEL, FJB and Nissl staining. However, ML221, an inhibitor of APJ, significantly reversed all the above neuroprotective effects of apelin-13. Moreover, a neuron-microglia co-culture system, which mimic SAH in vitro, confirmed the protective effect of apelin-13 on neurons and the inhibitory effect on inflammation through apoptosis-related proteins. CONCLUSIONS: These data demonstrated that apelin-13 exhibit a neuroprotective role after SAH through inhibition of apoptosis in an APJ dependent manner.
BACKGROUND: Early brain injury (EBI) has been considered as the major contributor to the neurological dysfunction and poor clinical outcomes of subarachnoid hemorrhage (SAH). Studies showed that apelin-13 exhibits a neuroprotective effect in brain damage induced by cerebral ischemia. However, it remains unclear whether apelin-13 could exhibit the protective functions following SAH. The present study aimed to validate the neuroprotective role of apelin-13 in SAH, and further investigated the underlying mechanisms. METHODS AND RESULTS: We constructed SAH rat model and we found that apelin-13 significantly alleviated neurological disorder and brain edema, improved memory deficits in SAH rats. Apelin-13 treatment decreased contents of TNF-α and IL-1β in cerebral spinal fluid of SAH rat by using ELISA. Apelin-13 treatment promoted the expression of APJ and Bcl-2, and decreased the level of active caspase-3 and Bax in the temporal cortex after SAH by using western blot. Also, apelin-13 attenuated the cortical cell death and neuronal degeneration as shown by TUNEL, FJB and Nissl staining. However, ML221, an inhibitor of APJ, significantly reversed all the above neuroprotective effects of apelin-13. Moreover, a neuron-microglia co-culture system, which mimic SAH in vitro, confirmed the protective effect of apelin-13 on neurons and the inhibitory effect on inflammation through apoptosis-related proteins. CONCLUSIONS: These data demonstrated that apelin-13 exhibit a neuroprotective role after SAH through inhibition of apoptosis in an APJ dependent manner.
Authors: Catharina Conzen; Katrin Becker; Walid Albanna; Miriam Weiss; Annika Bach; Nyanda Lushina; André Steimers; Sarah Pinkernell; Hans Clusmann; Ute Lindauer; Gerrit A Schubert Journal: Transl Stroke Res Date: 2018-11-15 Impact factor: 6.829