Cerebrovascular DiseaseIschemic brain edema☆
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).
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2020, CellCitation Excerpt :It is rapidly triggered when a state of hypoxia causes loss of energy-dependent solute homeostasis (Bordone et al., 2019). This drives water influx (Tang and Yang, 2016) down an osmotic gradient into perivascular astrocytes, causing them to swell (Rosenberg, 1999; Simard et al., 2007). The accumulation of intracellular water disrupts the local osmotic environment, resulting in ionic edema (Kawamata et al., 2007) and breakdown of the blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB), which may already be damaged by the initial injury.
Prognostic Significance of Plasma VEGFA and VEGFR2 in Acute Ischemic Stroke-a Prospective Cohort Study
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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].