INHIBITION OF PAR-2 ATTENUATES NEUROINFLAMMATION AND IMPROVES SHORT-TERM NEUROCOGNITIVE FUNCTIONS VIA ERK1/2 SIGNALING FOLLOWING ASPHYXIA-INDUCED CARDIAC ARREST IN RATS

Ocak U., Ocak P., Huang L., Zuo G., Yan J., Hu X., ...Daha Fazla

SHOCK, cilt.54, sa.4, ss.539-547, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 54 Sayı: 4
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1097/shk.0000000000001516
  • Dergi Adı: SHOCK
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.539-547
  • Anahtar Kelimeler: Cardiac arrest, global cerebral ischemia, neurocognitive, neuroinflammation, protease activated receptor 2, PROTEASE-ACTIVATED RECEPTORS, INTESTINAL ISCHEMIA-REPERFUSION, SUBARACHNOID HEMORRHAGE, COGNITIVE DYSFUNCTION, GLOBAL-ISCHEMIA, BRAIN, TRYPTASE, INJURY, PATHWAY, CELLS
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

Objective: Global cerebral ischemia-induced neuroinflammation causes neurofunctional impairment following cardiac arrest. Previous studies have demonstrated that the activation of protease-activated receptor-2 (PAR-2) contributes to neuroinflammation. In the present study, we aimed to determine the potential treatment effect of PAR-2 inhibition against neuroinflammation in the setting of asphyxial CA(ACA) in rats. Methods: A total of 116 adult, male Sprague-Dawley rats were randomly divided into Sham (n = 18) and ACA (n = 98) groups. Time course, short-term outcome, and mechanism studies were conducted. All drugs were delivered intranasally. The effect of PAR-2 inhibitor FSLLRY-NH2 on neurocognitive functions was assessed by neurologic deficit score, number of seizures, and T-maze test, while hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining after ACA. Western blotting was performed for the mechanism study at 24 h following ACA. Selective PAR-2 agonist (AC55541) and ERK1/2 inhibitor (PD98059) were used for intervention. Results: Inhibition of PAR-2 decreased neuroinflammation, reduced the number of degenerating hippocampal neurons and improved neurocognitive functions following ACA. PAR-2 activator alone exerted opposite effects to PAR-2 inhibitor. PAR-2mediated the augmented brain levels of proinflammatory cytokines by promoting the phosphorylation of ERK1/2. Conclusions: PAR-2 inhibition diminished neuroinflammation and thereby reduced hippocampal neuronal degeneration and neurocognitive impairment following ACA. This effect was at least partly mediated via the PAR-2/ERK1/2 signaling.