title: Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway.
abstract: Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Shanghai, 201112, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Miao
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Shanghai, 201112, China.
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Shanghai, 201112, China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Shanghai, 201112, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Shanghai, 201112, China. daijiong@126.com.
authors.forename: Jiong
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Shanghai, 200127, China. zxh196909@163.com.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control*; D057510:Endovascular Procedures / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011773:Pyruvates / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D011773:Pyruvates; C046522:ethyl pyruvate
keywords: Early brain injury (EBI); Ethyl pyruvate (EP); Jun N-terminal kinase (JNK); Subarachnoid hemorrhage (SAH); Tumor necrosis factor-α (TNF-α)