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Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: involvement of PI3K/Akt and ERK1/2 signaling pathway.
J Mol Neurosci. 2015 Apr; 55(4):912-22.JM

Abstract

Ischemic preconditioning (IPC) has been demonstrated to provide a neuroprotection against brain damage produced by focal cerebral ischemia. However, it is elusive whether ischemic preconditioning attenuates ischemic brain damage through modulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In the present study, we first explored the best scheme of repetitive ischemic preconditioning (RIPC) to protect rat brain against ischemic damage and then further investigated the underlying mechanisms in RIPC's neuroprotection. Adult male Sprague-Dawley rats underwent ischemic preconditioning or (and) middle cerebral artery occlusion (MCAO). LY294002 or (and) PD98059 were injected intracerebroventricularly to selectively inhibit the activation of PI3K/Akt or ERK1/2. Neurological deficit scores, cerebral infarct volume, and morphological characteristic were detected at corresponding time after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after cerebral ischemia. Expressions of p-Akt, t-Akt, p-ERK1/2, t-ERK1/2, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in ischemic brain were determined by Western blot. The release of tumor necrosis factor-α (TNF-α) in blood was examined by ELISA. In the various schemes of RIPC, IPC2 × 5 min causes less neuronal damage in the cortex and subcortex of ischemic brain and provides an obvious alleviation of cerebral infarction and neurological deficit after lethal ischemia. IPC2 × 5 min significantly reduces cerebral infarct volume, neurological deficit scores, and MPO activity; all of which were diminished by LY294002 or (and) PD98059. IPC2 × 5 min significantly upregulates the expressions of p-Akt and p-ERK1/2, which were inhibited by LY294002 or (and) PD98059. IPC2 × 5 min significantly downregulates the expressions of NF-κB p65 and COX-2 and attenuates the release of TNF-α; all of which were abolished by LY294002 or (and) PD98059. IPC2 × 5 min is the best scheme of RIPC to protect rat brain against cerebral ischemia. IPC2 × 5 min attenuates brain damage in rats subjected to lethal ischemia, and this neuroprotection is associated with inhibition of neuroinflammation through modulating PI3K/Akt and ERK1/2 signaling pathway.

Authors+Show Affiliations

Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, Fujian, 350001, China, unionnstu@hotmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25338292

Citation

Tu, Xian-kun, et al. "Repetitive Ischemic Preconditioning Attenuates Inflammatory Reaction and Brain Damage After Focal Cerebral Ischemia in Rats: Involvement of PI3K/Akt and ERK1/2 Signaling Pathway." Journal of Molecular Neuroscience : MN, vol. 55, no. 4, 2015, pp. 912-22.
Tu XK, Yang WZ, Chen JP, et al. Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: involvement of PI3K/Akt and ERK1/2 signaling pathway. J Mol Neurosci. 2015;55(4):912-22.
Tu, X. K., Yang, W. Z., Chen, J. P., Chen, Y., Chen, Q., Chen, P. P., & Shi, S. S. (2015). Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: involvement of PI3K/Akt and ERK1/2 signaling pathway. Journal of Molecular Neuroscience : MN, 55(4), 912-22. https://doi.org/10.1007/s12031-014-0446-9
Tu XK, et al. Repetitive Ischemic Preconditioning Attenuates Inflammatory Reaction and Brain Damage After Focal Cerebral Ischemia in Rats: Involvement of PI3K/Akt and ERK1/2 Signaling Pathway. J Mol Neurosci. 2015;55(4):912-22. PubMed PMID: 25338292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: involvement of PI3K/Akt and ERK1/2 signaling pathway. AU - Tu,Xian-kun, AU - Yang,Wei-zhong, AU - Chen,Jian-ping, AU - Chen,Yan, AU - Chen,Quan, AU - Chen,Ping-ping, AU - Shi,Song-sheng, Y1 - 2014/10/22/ PY - 2014/03/12/received PY - 2014/10/13/accepted PY - 2014/10/23/entrez PY - 2014/10/23/pubmed PY - 2015/12/15/medline SP - 912 EP - 22 JF - Journal of molecular neuroscience : MN JO - J Mol Neurosci VL - 55 IS - 4 N2 - Ischemic preconditioning (IPC) has been demonstrated to provide a neuroprotection against brain damage produced by focal cerebral ischemia. However, it is elusive whether ischemic preconditioning attenuates ischemic brain damage through modulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In the present study, we first explored the best scheme of repetitive ischemic preconditioning (RIPC) to protect rat brain against ischemic damage and then further investigated the underlying mechanisms in RIPC's neuroprotection. Adult male Sprague-Dawley rats underwent ischemic preconditioning or (and) middle cerebral artery occlusion (MCAO). LY294002 or (and) PD98059 were injected intracerebroventricularly to selectively inhibit the activation of PI3K/Akt or ERK1/2. Neurological deficit scores, cerebral infarct volume, and morphological characteristic were detected at corresponding time after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after cerebral ischemia. Expressions of p-Akt, t-Akt, p-ERK1/2, t-ERK1/2, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in ischemic brain were determined by Western blot. The release of tumor necrosis factor-α (TNF-α) in blood was examined by ELISA. In the various schemes of RIPC, IPC2 × 5 min causes less neuronal damage in the cortex and subcortex of ischemic brain and provides an obvious alleviation of cerebral infarction and neurological deficit after lethal ischemia. IPC2 × 5 min significantly reduces cerebral infarct volume, neurological deficit scores, and MPO activity; all of which were diminished by LY294002 or (and) PD98059. IPC2 × 5 min significantly upregulates the expressions of p-Akt and p-ERK1/2, which were inhibited by LY294002 or (and) PD98059. IPC2 × 5 min significantly downregulates the expressions of NF-κB p65 and COX-2 and attenuates the release of TNF-α; all of which were abolished by LY294002 or (and) PD98059. IPC2 × 5 min is the best scheme of RIPC to protect rat brain against cerebral ischemia. IPC2 × 5 min attenuates brain damage in rats subjected to lethal ischemia, and this neuroprotection is associated with inhibition of neuroinflammation through modulating PI3K/Akt and ERK1/2 signaling pathway. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/25338292/Repetitive_ischemic_preconditioning_attenuates_inflammatory_reaction_and_brain_damage_after_focal_cerebral_ischemia_in_rats:_involvement_of_PI3K/Akt_and_ERK1/2_signaling_pathway_ L2 - https://dx.doi.org/10.1007/s12031-014-0446-9 DB - PRIME DP - Unbound Medicine ER -