Published online before print January 6, 2005, doi: 10.1161/01.STR.0000153069.96296.fd
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(Stroke. 2005;36:189.)
© 2005 American Heart Association, Inc.
Advances in Stroke 2004 |
Exciting, Radical, Suicidal
How Brain Cells Die After Stroke
From the Neuroprotection Research Laboratory (E.H.L.), Departments of Radiology and Neurology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Charlestown, Mass; the Neurovascular Regulation and Stroke Laboratory (M.A.M.), Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; and the Neural Environment Cluster (T.P.J.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Eng H. Lo, Neuroprotection Research Laboratory, Harvard Medical School, MGH East 149-2401, Charlestown, MA 02129. E-mail Lo@helix.mgh.harvard.edu
Key Words: Advances in Stroke • apoptosis • erythopoietin • ischemia • neuroprotective agents
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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It is now widely accepted that not all brain cells die immediately after stroke. Surrounding a core of severe and rapid tissue injury, brain cell death evolves more slowly in a heterogeneous area that has been called the penumbra.1,2 In 1977, Astrup et al provided one of the first experimental demonstrations of the penumbra in a baboon model of cerebral artery occlusion.3 This region of brain in acute ischemic stroke was found to be electrically silent but sufficiently active metabolically to sustain membrane potentials. Neurons within the penumbra are functionally impaired but not yet dead. Without reperfusion, the penumbra collapses, brain cells die, and the lesion expands.
Although the precise timing and cellular pathways involved are not fully understood, it is believed that mechanisms actively promoting cell death are triggered after stroke. Remarkable progress has been made in dissecting these mechanisms over the past 3 decades. Three major pathways have emerged: excitotoxicity, oxidative stress, and apoptosis, and they are inextricably linked. Here, we explore the notion that stroke is most fruitfully investigated by an integrative "systems biology" approach that encompasses cell death and survival signaling within all components of the neurovascular unit.
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Cell Death: A Convergence of Factors |
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How do brain cells die after stroke? A large body of data suggest that it may be exciting (glutamate and excitotoxicity), radical (oxidative stress and free radicals), and suicidal (apoptotic-like pathways).4–6 Simply put, when brain fails to generate sufficient ATP, such as after oxygen and glucose deprivation, energy failure occurs and ionic gradients are lost. Glutamate is released,
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