title: Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation.
abstract: Acute inflammation plays an important role in the pathogenic progression of post-ischemic neuronal damage. Apelin-13 has been investigated as a neuropeptide for various neurological disorders. The present study was performed to evaluate the effects of apelin-13 on the inflammation of cerebral ischemia/reperfusion (I/R) injury. Transient focal I/R model in male Wistar rats were induced by 2h middle cerebral artery occlusion (MCAO) followed by 24h reperfusion. Rats then received treatment with apelin-13 or vehicle after ischemia at the onset of reperfusion. The neurological deficit was evaluated and the infarct volume was measured by TTC staining. The activity of myeloperoxidase (MPO) was measured. The expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) were measured using real-time PCR. And the expression of apelin receptor (APJ), ionized calcium-binding adapter molecule-1 (Iba1), glial fibrillary acidic protein (GFAP) and high mobility group box 1 (HMGB1) were measured by immunohistochemistry and western blot. Our results demonstrated that treatment with apelin-13 in I/R rats markedly reduced neurological deficits and the infarct volume. The increase of MPO activity induced by I/R was inhibited by apelin-13 treatment. The real-time PCR showed that apelin-13 decreased the expression of inflammatory cytokines such as IL-1β, TNF-α and ICAM-1 in I/R rats. The expression of APJ in I/R rats was increased. And the expression of Iba1, GFAP and HMGB1 in I/R rats was decreased by apelin-13 treatment indicating the inhibition of microglia, astrocytes and other inflammatory cells. In conclusion, apelin-13 is neuroprotective for neurons against I/R through inhibiting the neuroinflammation.
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China.
authors.forename: Yanyou
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Physiology, Taian Medical University, Taian 271000, PR China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Yang
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China. Electronic address: chenjnmc@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining 272067, PR China. Electronic address: baibo1@mail.jnmc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Bai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000075244:Apelin Receptors; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D000893:Anti-Inflammatory Agents; D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D009195:Peroxidase
keywords: Apelin-13; Cerebral ischemia; Inflammation; Neuroprotection