PMID- 31590996 OWN - NLM STAT- MEDLINE DCOM- 20200203 LR - 20200203 IS - 1532-8511 (Electronic) IS - 1052-3057 (Linking) VI - 28 IP - 12 DP - 2019 Dec TI - Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway. PG - 104375 LID - S1052-3057(19)30428-8 [pii] LID - 10.1016/j.jstrokecerebrovasdis.2019.104375 [doi] AB - BACKGROUND: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. MATERIALS AND METHODS: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-kappaB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat brain were examined by ELISA. RESULTS: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-kappaB p65, COX-2, TNF-alpha, and IL-1beta, all of which were inhibited by LY294002. CONCLUSION: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zhang, Hua-Bin AU - Zhang HB AD - Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China. FAU - Tu, Xian-Kun AU - Tu XK AD - Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China. Electronic address: unionnstu@hotmail.com. FAU - Chen, Quan AU - Chen Q AD - Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China. FAU - Shi, Song-Sheng AU - Shi SS AD - Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China. LA - eng PT - Journal Article DEP - 20191004 PL - United States TA - J Stroke Cerebrovasc Dis JT - Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association JID - 9111633 RN - 0 (Anti-Inflammatory Agents) RN - 0 (IL1B protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Neuroprotective Agents) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Rela protein, rat) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, rat) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - YI7VU623SF (Propofol) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Brain/*drug effects/enzymology/pathology MH - Brain Edema/enzymology/pathology/*prevention & control MH - Cyclooxygenase 2/metabolism MH - Disease Models, Animal MH - Encephalitis/enzymology/pathology/*prevention & control MH - Interleukin-1beta/metabolism MH - Male MH - NAD(P)H Dehydrogenase (Quinone)/metabolism MH - NF-E2-Related Factor 2/metabolism MH - Neuroprotective Agents/*pharmacology MH - Oxidative Stress/drug effects MH - Phosphatidylinositol 3-Kinase/*metabolism MH - Phosphorylation MH - Propofol/*pharmacology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Subarachnoid Hemorrhage/*drug therapy/enzymology/pathology MH - Transcription Factor RelA/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - PI3K/Akt OT - Subarachnoid hemorrhage OT - early brain injury OT - inflammation OT - oxidative stress OT - propofol EDAT- 2019/10/09 06:00 MHDA- 2020/02/06 06:00 CRDT- 2019/10/09 06:00 PHST- 2019/05/24 00:00 [received] PHST- 2019/08/04 00:00 [revised] PHST- 2019/08/26 00:00 [accepted] PHST- 2019/10/09 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2019/10/09 06:00 [entrez] AID - S1052-3057(19)30428-8 [pii] AID - 10.1016/j.jstrokecerebrovasdis.2019.104375 [doi] PST - ppublish SO - J Stroke Cerebrovasc Dis. 2019 Dec;28(12):104375. doi: 10.1016/j.jstrokecerebrovasdis.2019.104375. Epub 2019 Oct 4.