Elsevier

Progress in Cardiovascular Diseases

Volume 42, Issue 3, November–December 1999, Pages 209-216
Progress in Cardiovascular Diseases

Cerebrovascular Disease
Ischemic brain edema

https://doi.org/10.1016/S0033-0620(99)70003-4Get rights and content

Abstract

Brain edema is a life-threatening complication of cerebral infarction. The molecular cascade initiated by cerebral ischemia includes the loss of membrane ionic pumps and cell swelling. Secondary formation of free radicals and proteases disrupts brain-cell membranes, causing irreversible damage. New diagnostic methods based on magnetic resonance imaging have markedly improved diagnostic accuracy. Cytotoxic and vasogenic edema is maximal by 24 to 72 hours after the ischemic event. Thrombolytics reperfuse tissue and improve outcome; when treatment is delayed, they can increase edema and blood-brain barrier opening. Although osmotherapy reduces brain water, and is used to treat ischemic edema, its efficacy remains to be proven. As the molecular events become clearer, novel treatments that block different stages of the injury cascade will be available for clinical testing. Copyright © 1999 by W.B. Saunders Company

Progress in Cardiovascular Diseases, Vol. 42, No. 3 (November/December), 1999: pp 209-216

Section snippets

Molecular events in ischemia

The loss of oxygen and glucose, 2 essential substances for brain metabolism, disrupts the energy balance in brain cells. Energy substrates decrease, lactate builds up, free fatty acids are formed, and pH decreases.4 Membrane failure triggers the release of glutamate, opening channels for calcium entry.5 Sodium and calcium exchange pumps remove some of the calcium, but 3 sodium ions enter for every 2 calcium removed; cells swell as water is retained by the osmotic imbalance. Energy requiring

Computed tomography

Brain edema is seen on CT as an area of decreased attenuation because of the excess fluid. Urgent CT scans are routinely performed on stroke patients to rule out bleeding. This is particularly important in candidates for thrombolytic therapy.32 Signs of increased ICP and brain edema include effacement of the cortical sulci and distortion of the ventricles. Edema is generally absent from the CT for several days after a stroke. By 3 to 7 days, the region of the infarcted tissue can be

Thrombolysis and reperfusion injury

Treatment with recombinant tissue-type plasminogen activator (rt-PA) has been shown to reduce morbidity at 3 months compared with the placebo group.33 Although the study was positive, rt-PA increased the risk of intracranial bleeding. Of the patients given the placebo, less than 1% had symptomatic intracerebral hemorrhage, whereas the treated group had more than 6%. The risk of any hemorrhage was 11%, including asymptomatic patients with intracranial hemorrhage treated with rt-PA. Several

Treatment of ischemic edema

Although unproven, osmotherapy has been the mainstay of treatment of life-threatening cerebral edema since it was first introduced in 1962.34 Mannitol is used regularly, but there is little evidence that it has a beneficial effect in stroke. Glycerol had positive effects in stroke patients, but problems with the use of this agent have prevented its widespread use. Low doses of mannitol are advised to avoid electrolyte imbalance. These range from 0.5 to 1 gm/kg. Dehydration of tissues is

Summary

Ischemia initiates the molecular cascade of injury that starts with glutamate- and calcium-induced cell swelling. Immediate early genes are activated, leading to cytokine and free radical production. Inflammation begins early in the process with the activation of microglia cells and the recruitment of neutrophils. Eventually, the proteases begin the final assault on the cell that leads to cellular disruption with necrosis and apoptosis. Irreversible damage takes place once the proteases destroy

Acknowledgements

Studies in the author's laboratory were supported by grants from the Veterans Administration and the NIH (R01 NS21169).

References (37)

  • Z Huang et al.

    Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase

    Science

    (1994)
  • S Adler et al.

    Effect of acute hyponatremia on rat brain pH and rat brain buffering

    Am J Physiol

    (1989)
  • JC Ayus et al.

    Treatment of symptomatic hyponatremia and its relation to brain damage. A prospective study

    N Engl J Med

    (1987)
  • SR Levine et al.

    Prolonged deterioration of ischemic brain energy metabolism and acidosis associated with hyperglycemia: Human cerebral infarction studied by serial 31P NMR spectroscopy

    Ann Neurol

    (1988)
  • T Doczi et al.

    Brain water accumulation after the central administration of vasopressin

    Neurosurgery

    (1982)
  • RF Reeder et al.

    Effect of vasopressin on cold-induced brain edema in cats

    J Neurosurg

    (1986)
  • GA Rosenberg et al.

    Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats

    Stroke

    (1992)
  • JI Frank

    Large hemispheric infarction, deterioration, and intracranial pressure

    Neurology

    (1995)
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    Address reprint requests to Gary A. Rosenberg, MD, Department of Neurology, University of New Mexico, 915 Camino de Salud NE, Albuquerque, NM 87131; e-mail: [email protected].

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