caa a22 4500 606216200 CHVBK 20210128101102.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00701-015-2370-3 doi (NATIONALLICENCE)springer-10.1007/s00701-015-2370-3 Role of the AMPK signaling pathway in early brain injury after subarachnoid hemorrhage in rats [Elektronische Daten] [Ji-Yang An, Li-Li Zhou, Peng Sun, Hong-Gang Pang, Dan-Dong Li, Yu Li, Ming Zhang, Jin-Ning Song] Background: AMP-activated protein kinase (AMPK) is a key metabolic and stress sensor/effector. Few investigations have been performed to study the role of AMPK in subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was undertaken to investigate the time course of AMPK activation in the early stage of SAH and to evaluate the influence of AICAR (which is known to mimic AMP and activates AMPK) and compound C (a commonly used AMPK inhibitor) on EBI in rats following SAH. Methods: Adult male rats were divided into six groups: control, sham, SAH, SAH + vehicle, SAH + AICAR and SAH + compound C. SAHs were induced by a modified endovascular perforation method. Immunohistochemistry, real-time PCR and Western blot were used to detect the spatial and dynamic expression of AMPK after SAH. Cortical apoptosis and the expressions of apoptosis-related proteins such as FOXO3a (forkhead box, class O, 3a) and Bim (Bcl-2-interacting mediator of cell death) were detected after different drug interventions. Results: We found SAH induced prolonged activation of AMPK. Treatment with AICAR markedly induced overactivation of AMPK and upregulation of FOXO3a and Bim. AICAR also significantly exacerbated cerebral apoptosis and neurological impairment following SAH. On the other hand, pre-administration of compound C attenuated EBI in this SAH model by modulating cerebral apoptosis by inhibiting FOXO3a and Bim. Conclusions: Our findings suggest that the AMPK pathway may play an important role in SAH-induced neuronal apoptosis, and the use of AMPK inhibitors can provide neuroprotection in EBI after SAH. Springer-Verlag Wien, 2015 Subarachnoid hemorrhage nationallicence Early brain injury nationallicence Apoptosis nationallicence Adenosine monophosphate-activated protein kinase nationallicence Bim nationallicence An Ji-Yang Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Zhou Li-Li Department of General Surgery, the Second Affiliated Hospital of Medical College, Xi'an, Shaanxi, P. R. China aut Sun Peng Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Pang Hong-Gang Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Li Dan-Dong Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Li Yu Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Zhang Ming Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Song Jin-Ning Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut Acta Neurochirurgica Springer Vienna 157/5(2015-05-01), 781-792 0001-6268 157:5<781 2015 157 701 https://doi.org/10.1007/s00701-015-2370-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00701-015-2370-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- An Ji-Yang Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Zhou Li-Li Department of General Surgery, the Second Affiliated Hospital of Medical College, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Sun Peng Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Pang Hong-Gang Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Li Dan-Dong Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Li Yu Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Zhang Ming Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 700 1- Song Jin-Ning Department of Neurosurgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China aut NATIONALLICENCE 773 0- Acta Neurochirurgica Springer Vienna 157/5(2015-05-01), 781-792 0001-6268 157:5<781 2015 157 701