====== Thrombin in Intracerebral Hemorrhage ======


Previous studies demonstrated that thrombin is an important factor in [[brain injury]] after [[intracerebral hemorrhage]] and [[intraventricular hemorrhage]].

Intraventricular injection of thrombin causes significant [[hydrocephalus]] and white matter damage.

Results suggest decreasing CSF production by [[acetazolamide]] attenuated thrombin-induced hydrocephalus in rats
((Gao F, Zheng M, Hua Y, Keep RF, Xi G. Acetazolamide Attenuates
Thrombin-Induced Hydrocephalus. Acta Neurochir Suppl. 2016;121:373-7. doi:
10.1007/978-3-319-18497-5_64. PubMed PMID: 26463977.)).

Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral hemorrhage with aerobic capacity
((Ni W, Gao F, Zheng M, Koch LG, Britton SL, Keep RF, Xi G, Hua Y. Effects of
Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury. Acta 
Neurochir Suppl. 2016;121:379-84. doi: 10.1007/978-3-319-18497-5_65. PubMed PMID:
26463978.
)).

[[Thrombin]] is an essential component in the clotting cascade, and it is produced in the brain immediately after ICH induction
((Zheng, H., Chen, C., Zhang, J., Hu, Z. (2016). Mechanism and therapy of brain edema after intracerebral hemorrhage. Cerebrovasc. Dis. 42, 155–169. doi: 10.1159/000445170)).
However, thrombin can also participate in ICH-induced injury. The deleterious or protective effect of thrombin depends on its concentration
((Zhu, H., Wang, Z., Yu, J., Yang, X., He, F., Liu, Z., et al. (2019). Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage. Prog. Neurobiol. 178, 101610. doi: 10.1016/j.pneurobio.2019.03.003)).
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The potential mechanism of early [[edema]] around the clot is considered to be a vasogenic reaction to pro-osmotic substances such as [[electrolyte]]s and protein, which are released from the acute hematoma. This is followed by activation of the [[coagulation cascade]] and increased [[thrombin]] expression, which may propagate swelling. After the first week, any further edema is related to the cytotoxic effects of [[hemoglobin]] breakdown and the formation of [[reactive oxygen species]]
((Balami JS, Buchan AM. Complications of intracerebral haemorrhage. Lancet Neurol. 2012 Jan;11(1):101-18. doi: 10.1016/S1474-4422(11)70264-2. PMID: 22172625.)).
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[[Experiment]]al [[investigation]]s have indicated that [[thrombin]] formation, [[red blood cell]] lysis, and iron toxicity play a major role in ICH-induced injury and that these mechanisms may provide new therapeutic targets
((Hua Y, Keep RF, Hoff JT, Xi G. Brain injury after intracerebral hemorrhage: the role of thrombin and iron. Stroke. 2007 Feb;38(2 Suppl):759-62. doi: 10.1161/01.STR.0000247868.97078.10. PMID: 17261733.)).