The Ischemic Penumbra: Identification, Evolution and Treatment Concepts

The concept of the ischemic penumbra is an important one for both basic investigators of cerebral ischemia and for clinicians who treat stroke patients. The ischemic penumbra has been defined in a variety of ways, but the most clinically relevant definition is that portion of the ischemic territory that is still potentially salvageable, if an appropriate treatment is given. Currently, three main challenges persist for those interested in the ischemic penumbra concept: how can this ischemic region be most accurately identified in stroke patients, what mechanisms of ischemic cell death are most important for progression from penumbra towards irreversible injury and what therapeutic modalities are most likely to impede the development of infarction? Much important information regarding each of these topics has become available recently and will be the focus of this paper.

[1]  S. Warach,et al.  Effect of citicoline on ischemic lesions as measured by diffusion‐weighted magnetic resonance imaging , 2000 .

[2]  G. Schlaug,et al.  The ischemic penumbra: operationally defined by diffusion and perfusion MRI. , 1999, Neurology.

[3]  V Beaudouin,et al.  Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. , 1996, Stroke.

[4]  H. Yonas,et al.  Advanced CT imaging (functional CT). , 1999, Neuroimaging clinics of North America.

[5]  G. Mies,et al.  Ischemic Thresholds of Cerebral Protein Synthesis and Energy State following Middle Cerebral Artery Occlusion in Rat , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  K Ohta,et al.  Repeat Positron Emission Tomographic Studies in Transient Middle Cerebral Artery Occlusion in Cats: Residual Perfusion and Efficacy of Postischemic Reperfusion , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[8]  C. Chung,et al.  Triphasic perfusion computed tomography in acute middle cerebral artery stroke: a correlation with angiographic findings. , 2000, Archives of neurology.

[9]  M E Moseley,et al.  New magnetic resonance imaging methods for cerebrovascular disease: Emerging clinical applications , 2000, Annals of neurology.

[10]  S. Lipton,et al.  Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial function , 1995, Neuron.

[11]  A. Mendelow,et al.  Early computed-tomography abnormalities in acute stroke , 1997, The Lancet.

[12]  G. Semenza,et al.  HIF-1, O2, and the 3 PHDs How Animal Cells Signal Hypoxia to the Nucleus , 2001, Cell.

[13]  Tak W. Mak,et al.  Two Distinct Pathways Leading to Nuclear Apoptosis , 2000, The Journal of experimental medicine.

[14]  Matthias Koenig,et al.  Quantitative Assessment of the Ischemic Brain by Means of Perfusion-Related Parameters Derived From Perfusion CT , 2001, Stroke.

[15]  R. Oppenheim,et al.  Programmed Cell Death in the Developing Nervous System , 1996, Brain pathology.

[16]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[17]  Jun Chen,et al.  Programmed Cell Death in Cerebral Ischemia , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  K. I. Maynard,et al.  Neuroprotection against Ischemia by Metabolic Inhibition Revisited: A Comparison of Hypothermia, a Pharmacologic Cocktail and Magnesium Plus Mexiletine , 1999, Annals of the New York Academy of Sciences.

[19]  Stephen Rose,et al.  Diffusion‐ and perfusion‐weighted MRI response to thrombolysis in stroke , 2002, Annals of neurology.

[20]  Z. Ke.  Mapping the ischemic penumbra with PET , 2000 .

[21]  K. Hossmann.  Viability thresholds and the penumbra of focal ischemia , 1994, Annals of neurology.

[22]  Julio H. Garcia,et al.  Mechanisms of Neuronal Cell Death After Ischemic Injury to the Brain , 2001 .

[23]  A. Hakim.  The Cerebral Ischemic Penumbra , 1987, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[24]  W Hacke,et al.  Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia , 2001, Annals of neurology.

[25]  D. Levy,et al.  Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. , 2000, JAMA.

[26]  Jean-Philippe Thiran,et al.  Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients , 2002, Annals of neurology.

[27]  B. Siesjö,et al.  Calcium in ischemic cell death. , 1998, Stroke.

[28]  J D Fenstermacher,et al.  Secondary decline in apparent diffusion coefficient and neurological outcomes after a short period of focal brain ischemia in rats , 2000, Annals of neurology.

[29]  K Wienhard,et al.  Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke. , 1998, Stroke.

[30]  Fausto Viader,et al.  Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra , 1996, Annals of neurology.

[31]  M. Fisher,et al.  An overview of acute stroke therapy: past, present, and future. , 2000, Archives of internal medicine.

[32]  Gary Duckwiler,et al.  Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging , 2000, Annals of neurology.