New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies.
Intracerebral hemorrhage (ICH) remains a major medical problem, for which there is no effective treatment. However, extensive experimental and clinical research carried out in recent years has brought to light new exciting ideas for novel potential treatments. First, it was well documented that the management of hypertension helps to prevent new and recurrent ICH. Also, development of new guidelines for management of hypertension after the onset of the ICH may help in more effective ICH treatment. Existing contemporary data collected from preclinical studies indicates that ICH-induced inflammation represents a key factor leading to secondary brain damage, suggesting that some anti-inflammatory approaches can be used to treat hemorrhagic stroke. In this article, beyond discussing implications related to hypertension, we will summarize important (but not all) new discoveries connecting the role of inflammation to ICH pathology. Selected aspects of inflammatory response including the role of cytokines, transcription factor nuclear factor-kB, microglia activation, astrogliosis, and complement activation will be introduced. We will also discuss the role for reactive oxygen species and metalloproteinases in ICH pathogenesis and introduce basic knowledge on the nature of ICH-induced cell death including apoptosis. Potential targets for intervention and translation will be discussed.
Aronowski
Jaroslaw
J
Stroke Program, Department of Neurology, University of Texas-Houston Medical School, Houston, TX 77030, USA. j.aronowski@uth.tmc.edu
Hall
Christiana E
CE
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000503:physiopathology* / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D017628:Microglia / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases