Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

被引:79
作者
Belur, Praveen K. [1 ]
Chang, Jason J. [2 ]
He, Shuhan [1 ]
Emanuel, Benjamin A. [2 ]
Mack, William J. [3 ]
机构
[1] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA
[2] Univ So Calif, Dept Neurol, Div Neurocrit Care Stroke, Los Angeles, CA USA
[3] Univ So Calif, Dept Neurosurg, Los Angeles, CA USA
关键词
intracerebral hemorrhage; secondary brain injury; pathophysiology; therapeutic intervention; animal model; neuroprotection; COLONY-STIMULATING FACTOR; DELAYED POSTISCHEMIC HYPOTHERMIA; BLOOD-PRESSURE REDUCTION; ACTIVATED FACTOR-VII; PRIOR STATIN USE; RAT MODEL; NEUROLOGICAL DEFICITS; SENSORIMOTOR RECOVERY; INDUCED ATTENUATION; IRON ACCUMULATION;
D O I
10.3171/2013.2.FOCUS1317
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.
引用
收藏
页数:8
相关论文
共 96 条
[1]
Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial [J].
Anderson, Craig S. ;
Huang, Yining ;
Wang, Ji Guang ;
Arima, Hisatomi ;
Neal, Bruce ;
Peng, Bin ;
Heeley, Emma ;
Skulina, Christian ;
Parsons, Mark W. ;
Kim, Jong Sung ;
Tao, Qing Ling ;
Li, Yue Chun ;
Jiang, Jian Dong ;
Tai, Li Wen ;
Zhang, Jin Li ;
Xu, En ;
Cheng, Yan ;
Heritier, Stephan ;
Morgenstern, Lewis B. ;
Chalmers, John .
LANCET NEUROLOGY, 2008, 7 (05) :391-399
[2]
Effects of Early Intensive Blood Pressure-Lowering Treatment on the Growth of Hematoma and Perihematomal Edema in Acute Intracerebral Hemorrhage The Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) [J].
Anderson, Craig S. ;
Huang, Yining ;
Arima, Hisatomi ;
Heeley, Emma ;
Skulina, Christian ;
Parsons, Mark W. ;
Peng, Bin ;
Li, Qiang ;
Su, Steve ;
Tao, Qing Ling ;
Li, Yue Chun ;
Jiang, Jian Dong ;
Tai, Li Wen ;
Zhang, Jin Li ;
Xu, En ;
Cheng, Yan ;
Morgenstern, Lewis B. ;
Chalmers, John ;
Wang, Ji Guang .
STROKE, 2010, 41 (02) :307-312
[3]
Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome [J].
Auriat, Angela M. ;
Silasi, Gergely ;
Wei, Zhouping ;
Paquette, Rosalie ;
Paterson, Phyllis ;
Nichol, Helen ;
Colbourne, Frederick .
EXPERIMENTAL NEUROLOGY, 2012, 234 (01) :136-143
[4]
Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention [J].
Babu, Ranjith ;
Bagley, Jacob H. ;
Di, Chunhui ;
Friedm, Allan H. ;
Adamson, Cory .
NEUROSURGICAL FOCUS, 2012, 32 (04)
[5]
Inflammatory mediators and stroke: New opportunities for novel therapeutics [J].
Barone, FC ;
Feuerstein, GZ .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (08) :819-834
[6]
Long-term histological and behavioural characterisation of a collagenase-induced model of intracerebral haemorrhage in rats [J].
Beray-Berthat, Virginie ;
Delifer, Celine ;
Besson, Valerie C. ;
Girgis, Haymen ;
Coqueran, Berard ;
Plotkine, Michel ;
Marchand-Leroux, Catherine ;
Margaill, Isabelle .
JOURNAL OF NEUROSCIENCE METHODS, 2010, 191 (02) :180-190
[7]
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia [J].
Bernard, SA ;
Gray, TW ;
Buist, MD ;
Jones, BM ;
Silvester, W ;
Gutteridge, G ;
Smith, K .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (08) :557-563
[8]
ULTRA-EARLY EVALUATION OF INTRACEREBRAL HEMORRHAGE [J].
BRODERICK, JP ;
BROTT, TG ;
TOMSICK, T ;
BARSAN, W ;
SPILKER, J .
JOURNAL OF NEUROSURGERY, 1990, 72 (02) :195-199
[9]
Prolonged but delayed postischemic hypothermia: A long-term outcome study in the rat middle cerebral artery occlusion model [J].
Colbourne, F ;
Corbett, D ;
Zhao, ZH ;
Yang, J ;
Buchan, AM .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (12) :1702-1708
[10]
COLBOURNE F, 1995, J NEUROSCI, V15, P7250