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Course: MCAT > Unit 2

Lesson 3: Foundation 3: Organ Systems

Nervous system: Effects of stroke on the brain

Problem

Following cerebral ischemia (stroke), cell swelling is the earliest morphological change in injured neuronal, glial and endothelial cells. Cell swelling results from increased Na+ and Ca2+ influx into the cytosol via ionic mechanisms invoked by membrane depolarization and several harmful factors, such as reactive oxygen species (ROS). During the sub-acute and chronic phases after ischemia, injured cells may also show a phenotype of cell shrinkage due to complex processes involving membrane receptors/channels and programmed cell death signals. Accumulating evidence supports a key role of energy deficiency and dysfunction of Na+/K+-ATPase in ischemia-induced cell volume changes and cell death.
Figure 1 illustrates a simplified model of ischemia-induced neuronal cell death. Excessive activation of Ca2+ and Na+ permeable channels and receptors leads to intracellular Ca2+ and Na+ accumulation. The resulting cell swelling and destructive consequences are characteristics of necrosis. On the other hand, ischemia can cause over-activation of K+ permeable channels and receptors that mediate pro-apoptotic K+ efflux. The resulted intracellular K+ reduction consequently induces caspase activation and apoptotic cell death. Concurrent activation of these cell death events likely occurs after an ischemic insult and may result in hybrid cell death features in the same cells. The dysfunction of Na+/K+ pump plays a critical role in the development of hybrid cell death. Recent data suggest that excessive autophage also contributes to ischemic cellular damage and is an integrated component of hybrid cell death.
Figure 1 Cellular changes following a stroke
A researcher studying the effects of ischemic stroke on interstitial fluid composition induces focal ischemia in the brains of mice, then samples the interstitial fluid at various time points after ischemia to analyze it for the concentrations of ions and other constituents. The researcher hypothesizes that the extracellular concentration of potassium ions will rise following ischemia, followed by an eventual return to normal. The researcher further hypothesizes that the concentration of the protein albumin in the brain, which is normally found at a much lower concentration in the brain than in the blood, will also rise following ischemia, followed by an eventual return to normal.
Adapted from Song M, Yu SP. Ionic regulation of cell volume changes and cell death after ischemic stroke. Transl Stroke Res. 2014 Feb;5(1):17-27. doi: 10.1007/s12975-013-0314-x. Epub 2013 Dec 7. PMID: 24323733; PMCID: PMC3978072.
A rise in albumin concentration in the brain would contribute to which of the following effects following stroke?
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