Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages - PubMed (original) (raw)
Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages
Xiurong Zhao et al. Ann Neurol. 2007 Apr.
Abstract
Objective: Phagocytosis is necessary to eliminate the hematoma after intracerebral hemorrhage (ICH); however, release of proinflammatory mediators and free radicals during phagocyte activation is toxic to neighboring cells, leading to secondary brain injury. Promotion of phagocytosis in a timely and efficient manner may limit the toxic effects of persistent blood products on surrounding tissue and may be important for recovery after ICH.
Methods: Intrastriatal blood injection in rodents and primary microglia in culture exposed to red blood cells were used to model ICH and to study mechanisms of hematoma resolution and phagocytosis regulation by peroxisome proliferator-activated receptor gamma (PPARgamma) in microglia/macrophages.
Results: Our study demonstrated that the PPARgamma agonist, rosiglitazone, promoted hematoma resolution, decreased neuronal damage, and improved functional recovery in a mouse ICH model. Microglia isolated from murine brains showed more efficient phagocytosis in response to PPARgamma activators. PPARgamma activators significantly increased PPARgamma-regulated gene (catalase and CD36) expression, whereas reducing proinflammatory gene (tumor necrosis factor-alpha, interleukin-1beta, matrix metalloproteinase-9, and inducible nitric oxide synthase) expression, extracellular H(2)O(2) level, and neuronal damage. Phagocytosis by microglia was significantly inhibited by PPARgamma gene knockdown or neutralizing anti-CD36 antibody, whereas it was enhanced by exogenous catalase.
Interpretation: PPARgamma in macrophages acts as an important factor in promoting hematoma absorption and protecting other brain cells from ICH-induced damage.
Similar articles
- Hematoma resolution as a therapeutic target: the role of microglia/macrophages.
Zhao X, Grotta J, Gonzales N, Aronowski J. Zhao X, et al. Stroke. 2009 Mar;40(3 Suppl):S92-4. doi: 10.1161/STROKEAHA.108.533158. Epub 2008 Dec 8. Stroke. 2009. PMID: 19064796 - Neuroprotection against focal ischemic brain injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.
Luo Y, Yin W, Signore AP, Zhang F, Hong Z, Wang S, Graham SH, Chen J. Luo Y, et al. J Neurochem. 2006 Apr;97(2):435-48. doi: 10.1111/j.1471-4159.2006.03758.x. Epub 2006 Mar 15. J Neurochem. 2006. PMID: 16539667 - Pleiotropic role of PPARγ in intracerebral hemorrhage: an intricate system involving Nrf2, RXR, and NF-κB.
Zhao XR, Gonzales N, Aronowski J. Zhao XR, et al. CNS Neurosci Ther. 2015 Apr;21(4):357-66. doi: 10.1111/cns.12350. Epub 2014 Nov 28. CNS Neurosci Ther. 2015. PMID: 25430543 Free PMC article. Review. - Peroxisome proliferator-activated receptor gamma (PPAR gamma) and sepsis.
von Knethen A, Soller M, Brüne B. von Knethen A, et al. Arch Immunol Ther Exp (Warsz). 2007 Jan-Feb;55(1):19-25. doi: 10.1007/s00005-007-0005-y. Arch Immunol Ther Exp (Warsz). 2007. PMID: 17277894 Review.
Cited by
- Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage.
Cao S, Zheng M, Hua Y, Chen G, Keep RF, Xi G. Cao S, et al. Stroke. 2016 Jun;47(6):1626-31. doi: 10.1161/STROKEAHA.116.013146. Epub 2016 Apr 28. Stroke. 2016. PMID: 27125525 Free PMC article. - The Role of Oxidative Stress in the Progression of Secondary Brain Injury Following Germinal Matrix Hemorrhage.
Nour Eldine M, Alhousseini M, Nour-Eldine W, Noureldine H, Vakharia KV, Krafft PR, Noureldine MHA. Nour Eldine M, et al. Transl Stroke Res. 2024 Jun;15(3):647-658. doi: 10.1007/s12975-023-01147-3. Epub 2023 Mar 17. Transl Stroke Res. 2024. PMID: 36930383 Review. - Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage.
Chang CF, Massey J, Osherov A, Angenendt da Costa LH, Sansing LH. Chang CF, et al. Stroke. 2020 Feb;51(2):612-618. doi: 10.1161/STROKEAHA.119.027037. Epub 2019 Dec 12. Stroke. 2020. PMID: 31826730 Free PMC article. - Molecular pathophysiology of cerebral hemorrhage: secondary brain injury.
Aronowski J, Zhao X. Aronowski J, et al. Stroke. 2011 Jun;42(6):1781-6. doi: 10.1161/STROKEAHA.110.596718. Epub 2011 Apr 28. Stroke. 2011. PMID: 21527759 Free PMC article. Review. - Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage: an intrinsic review of a hematoma resolving pathway.
Flores J, Tang J. Flores J, et al. Neural Regen Res. 2024 Feb;19(2):350-354. doi: 10.4103/1673-5374.379040. Neural Regen Res. 2024. PMID: 37488889 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources