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An Update on Inflammation in the Acute Phase of Intracerebral Hemorrhage

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Abstract

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder, which is associated with high rates of mortality and morbidity. Despite extensive research into the pathology of ICH, there are still no clinically approved neuroprotective treatments. Currently, increasing evidence has shown that inflammatory responses participate in the pathophysiological processes of brain injury following ICH. In this editorial, we summarized some promising advances in the field of inflammation and ICH, which contained animal and human investigations; discussed the role of neuroinflammation, systemic inflammatory responses, and some potential targets; and focused on the challenges of translation between pre-clinical and clinical studies and potential anti-inflammatory therapeutic approaches after ICH.

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References

  1. Pandey AS, Xi G. Intracerebral hemorrhage: a multimodality approach to improving outcome. Transl Stroke Res. 2014;5(3):313–5. doi:10.1007/s12975-014-0344-z.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Chen Q, Zhang J, Guo J, Tang J, Tao Y, Li L, et al. Chronic hydrocephalus and perihematomal tissue injury developed in a rat model of intracerebral hemorrhage with ventricular extension. Transl Stroke Res. 2014. doi:10.1007/s12975-014-0367-5.

    PubMed Central  Google Scholar 

  3. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31. doi:10.1016/S1474-4422(12)70104-7.

    Article  CAS  PubMed  Google Scholar 

  4. Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115:25–44. doi:10.1016/j.pneurobio.2013.11.003.

    Article  CAS  PubMed  Google Scholar 

  5. Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365(9457):387–97. doi:10.1016/S0140-6736(05)17826-X.

    Article  PubMed  Google Scholar 

  6. Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382(9890):397–408. doi:10.1016/S0140-6736(13)60986-1.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Wu L, Walas S, Leung W, Sykes DB, Wu J, Lo EH, et al. Neuregulin1-beta decreases IL-1beta-induced neutrophil adhesion to human brain microvascular endothelial cells. Transl Stroke Res. 2014. doi:10.1007/s12975-014-0347-9.

    Google Scholar 

  8. An C, Shi Y, Li P, Hu X, Gan Y, Stetler RA, et al. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair. Prog Neurobiol. 2014;115:6–24. doi:10.1016/j.pneurobio.2013.12.002.

    Article  CAS  PubMed  Google Scholar 

  9. Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Khodadadi B, Jazayeri S, et al. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci. 2014. doi:10.1179/1476830513Y.0000000106.

    Google Scholar 

  10. Theadom A, Mahon S, Barker-Collo S, McPherson K, Rush E, Vandal AC, et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol Off J Eur Fed Neurol Soc. 2013;20(8):1135–44. doi:10.1111/ene.12099.

    CAS  Google Scholar 

  11. Zhao X, Sun G, Ting SM, Song S, Zhang J, Edwards NJ, et al. Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance. J Neurochem. 2014. doi:10.1111/jnc.12974.

    Google Scholar 

  12. Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007;61(4):352–62. doi:10.1002/ana.21097.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou QB, Jin YL, Jia Q, Zhang Y, Li LY, Liu P, et al. Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage. Inflammation. 2014;37(1):107–15. doi:10.1007/s10753-013-9717-9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Sun H, Tang Y, Guan X, Li L, Wang D. Effects of selective hypothermia on blood–brain barrier integrity and tight junction protein expression levels after intracerebral hemorrhage in rats. Biol Chem. 2013;394(10):1317–24. doi:10.1515/hsz-2013-0142.

    Article  CAS  PubMed  Google Scholar 

  15. Yang Z, Zhao T, Zou Y, Zhang JH, Feng H. Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage. Immunol Lett. 2014;160(1):89–95. doi:10.1016/j.imlet.2014.03.005.

    Article  CAS  PubMed  Google Scholar 

  16. Baroja-Mazo A, Martin-Sanchez F, Gomez AI, Martinez CM, Amores-Iniesta J, Compan V, et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 2014;15(8):738–48. doi:10.1038/ni.2919.

    Article  CAS  PubMed  Google Scholar 

  17. Ma Q, Chen S, Hu Q, Feng H, Zhang JH, Tang J. NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage. Ann Neurol. 2014;75(2):209–19. doi:10.1002/ana.24070.

    Article  CAS  PubMed  Google Scholar 

  18. Yao Y, Tsirka SE. Chemokines and their receptors in intracerebral hemorrhage. Transl Stroke Res. 2012;3 Suppl 1:70–9. doi:10.1007/s12975-012-0155-z.

    Article  CAS  PubMed  Google Scholar 

  19. Matsushita H, Hijioka M, Ishibashi H, Anan J, Kurauchi Y, Hisatsune A, et al. Suppression of CXCL2 upregulation underlies the therapeutic effect of the retinoid Am80 on intracerebral hemorrhage in mice. J Neurosci Res. 2014;92(8):1024–34. doi:10.1002/jnr.23379.

    Article  CAS  PubMed  Google Scholar 

  20. Hammond MD, Taylor RA, Mullen MT, Ai Y, Aguila HL, Mack M, et al. CCR2+ Ly6C(hi) inflammatory monocyte recruitment exacerbates acute disability following intracerebral hemorrhage. J Neurosci Off J Soc Neurosci. 2014;34(11):3901–9. doi:10.1523/JNEUROSCI. 4070-13.2014.

    Article  CAS  Google Scholar 

  21. Zhou X, Xie Q, Xi G, Keep RF, Hua Y. Brain CD47 expression in a swine model of intracerebral hemorrhage. Brain Res. 2014;1574:70–6. doi:10.1016/j.brainres.2014.06.003.

    Article  CAS  PubMed  Google Scholar 

  22. Hosaka K, Hoh BL. Inflammation and cerebral aneurysms. Transl Stroke Res. 2014;5(2):190–8. doi:10.1007/s12975-013-0313-y.

    Article  CAS  PubMed  Google Scholar 

  23. Rolland WB, Lekic T, Krafft PR, Hasegawa Y, Altay O, Hartman R, et al. Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage. Exp Neurol. 2013;241:45–55. doi:10.1016/j.expneurol.2012.12.009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Zhao X, Sun G, Zhang H, Ting SM, Song S, Gonzales N, et al. Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage. Transl Stroke Res. 2014;5(5):554–61. doi:10.1007/s12975-014-0341-2.

    Article  PubMed  Google Scholar 

  25. Wu LJ. Microglial voltage-gated proton channel Hv1 in ischemic stroke. Transl Stroke Res. 2014;5(1):99–108. doi:10.1007/s12975-013-0289-7.

    Article  CAS  PubMed  Google Scholar 

  26. Agnihotri S, Czap A, Staff I, Fortunato G, McCullough LD. Peripheral leukocyte counts and outcomes after intracerebral hemorrhage. J Neuroinflammation. 2011;8:160. doi:10.1186/1742-2094-8-160.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Sun W, Peacock A, Becker J, Phillips-Bute B, Laskowitz DT, James ML. Correlation of leukocytosis with early neurological deterioration following supratentorial intracerebral hemorrhage. J Clin Neurosci Off J Neurosurg Soc Australas. 2012;19(8):1096–100. doi:10.1016/j.jocn.2011.11.020.

    Google Scholar 

  28. Silva Y, Leira R, Tejada J, Lainez JM, Castillo J, Davalos A. Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. Stroke J Cereb Circ. 2005;36(1):86–91. doi:10.1161/01.STR.0000149615.51204.0b.

    Article  Google Scholar 

  29. Hammond MD, Ambler WG, Ai Y, Sansing LH. alpha4 integrin is a regulator of leukocyte recruitment after experimental intracerebral hemorrhage. Stroke J Cereb Circ. 2014;45(8):2485–7. doi:10.1161/STROKEAHA.114.005551.

    Article  CAS  Google Scholar 

  30. Xu C, Wang T, Cheng S, Liu Y. Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice. J Neuroinflammation. 2013;10:141. doi:10.1186/1742-2094-10-141.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Fu Y, Hao J, Zhang N, Ren L, Sun N, Li YJ, et al. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014;71(9):1092–101. doi:10.1001/jamaneurol.2014.1065.

    Article  PubMed  Google Scholar 

  32. Adeoye O, Walsh K, Woo JG, Haverbusch M, Moomaw CJ, Broderick JP, et al. Peripheral monocyte count is associated with case fatality after intracerebral hemorrhage. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc. 2014;23(2):e107–11. doi:10.1016/j.jstrokecerebrovasdis.2013.09.006.

    Article  Google Scholar 

  33. Pennypacker KR. Targeting the peripheral inflammatory response to stroke: role of the spleen. Transl Stroke Res. 2014;5(6):635–7. doi:10.1007/s12975-014-0372-8.

    Article  PubMed  Google Scholar 

  34. Heiman A, Pallottie A, Heary RF, Elkabes S. Toll-like receptors in central nervous system injury and disease: a focus on the spinal cord. Brain Behav Immun. 2014. doi:10.1016/j.bbi.2014.06.203.

    PubMed  Google Scholar 

  35. Wang YC, Wang PF, Fang H, Chen J, Xiong XY, Yang QW. Toll-like receptor 4 antagonist attenuates intracerebral hemorrhage-induced brain injury. Stroke J Cereb Circ. 2013;44(9):2545–52. doi:10.1161/STROKEAHA.113.001038.

    Article  CAS  Google Scholar 

  36. Wang YC, Zhou Y, Fang H, Lin S, Wang PF, Xiong RP, et al. Toll-like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage. Ann Neurol. 2014;75(6):876–89. doi:10.1002/ana.24159.

    Article  CAS  PubMed  Google Scholar 

  37. Fang H, Chen J, Lin S, Wang P, Wang Y, Xiong X, et al. CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling. J Immunol. 2014;192(12):5984–92. doi:10.4049/jimmunol.1400054.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Rodriguez-Yanez M, Brea D, Arias S, Blanco M, Pumar JM, Castillo J, et al. Increased expression of Toll-like receptors 2 and 4 is associated with poor outcome in intracerebral hemorrhage. J Neuroimmunol. 2012;247(1–2):75–80. doi:10.1016/j.jneuroim.2012.03.019.

    Article  CAS  PubMed  Google Scholar 

  39. Shin HJ, Youn HS. TBK1-targeted suppression of TRIF-dependent signaling pathway of Toll-like receptors by helenalin. Life Sci. 2013;93(22):847–54. doi:10.1016/j.lfs.2013.09.004.

    Article  CAS  PubMed  Google Scholar 

  40. Zhou Y, Xiong KL, Lin S, Zhong Q, Lu FL, Liang H, et al. Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage. Mediat Inflamm. 2010. doi:10.1155/2010/142458.

    Google Scholar 

  41. Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke J Cereb Circ. 2011;42(6):1781–6. doi:10.1161/STROKEAHA.110.596718.

    Article  Google Scholar 

  42. Gonzales NR, Shah J, Sangha N, Sosa L, Martinez R, Shen L, et al. Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC). Int J Stroke Off J Int Stroke Soc. 2013;8(5):388–96. doi:10.1111/j.1747-4949.2011.00761.x.

    Article  Google Scholar 

  43. Cheng Y, Xi G, Jin H, Keep RF, Feng J, Hua Y. Thrombin-induced cerebral hemorrhage: role of protease-activated receptor-1. Transl Stroke Res. 2014;5(4):472–5. doi:10.1007/s12975-013-0288-8.

    Article  CAS  PubMed  Google Scholar 

  44. Xiong XY, Wang J, Qian ZM, Yang QW. Iron and intracerebral hemorrhage: from mechanism to translation. Transl Stroke Res. 2014;5(4):429–41. doi:10.1007/s12975-013-0317-7.

    Article  CAS  PubMed  Google Scholar 

  45. Zhao J, Chen Z, Xi G, Keep RF, Hua Y. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res. 2014;5(5):586–94. doi:10.1007/s12975-014-0353-y.

    Article  CAS  PubMed  Google Scholar 

  46. Shichita T, Ito M, Yoshimura A. Post-ischemic inflammation regulates neural damage and protection. Front Cell Neurosci. 2014;8:319. doi:10.3389/fncel.2014.00319.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. Microglial and macrophage polarization-new prospects for brain repair. Nat Rev Neurol. 2014. doi:10.1038/nrneurol.2014.207.

    PubMed  Google Scholar 

  48. Hu X, Liou AK, Leak RK, Xu M, An C, Suenaga J, et al. Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles. Prog Neurobiol. 2014;119–120:60–84. doi:10.1016/j.pneurobio.2014.06.002.

    Article  PubMed  Google Scholar 

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Compliance with Ethics Requirements

The study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University. This article does not contain any studies with human or animal subjects.

Conflict of Interest

Sheng Chen declares that he has no conflict of interest. Qingwu Yang declares that he has no conflict of interest. Gang Chen declares that he has no conflict of interest. John H. Zhang declares that he has no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

    Sheng Chen

  2. Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Qingwu Yang

  3. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China

    Gang Chen

  4. Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

    John H. Zhang

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  1. Sheng Chen
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  2. Qingwu Yang
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Correspondence to Gang Chen.

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Chen, S., Yang, Q., Chen, G. et al. An Update on Inflammation in the Acute Phase of Intracerebral Hemorrhage. Transl. Stroke Res. 6, 4–8 (2015). https://doi.org/10.1007/s12975-014-0384-4

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  • DOI: https://doi.org/10.1007/s12975-014-0384-4

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