9/17/2012

Acclimation to hypoxia protects brain tissue against the effects of a stroke


Stroke refers to ischemic conditions where blood flow to brain tissue is significantly reduced (typically when a clot blocks one of the arteries) causing lack of oxygen that results in destruction of brain tissue. Stroke currently constitutes one of the most severe medical problems, with one-third of deaths in Western societies being caused by stroke. Measures have been targeted to preventing / reducing the number of strokes (e.g., providing public information on factors elevating the risk for stroke and medically intervening when high blood pressure is detected), development of treatments that reduce brain damage caused by strokes (e.g., administration of clot-dissolving agents within three hours from the occurrence of a stroke), and rehabilitation methods. In addition to these, there is also research on ways to mitigate the damaging effects of stroke/ischemia.

In their recent study, Dunn et al. (2012) tested whether exposing experimental animals to hypoxia (i.e., keeping the experimental animals in chambers with half of the normal atmospheric pressure) over longer periods of time (in their study three weeks) reduces the effects of an experimentally induced stroke (occlusion of middle cerebral artery for 60 minutes). The authors note that hypoxia acclimation has been previously shown to induce changes that improve the capacity of tissue to survive low oxygen conditions, including increased capacity to supply oxygen (i.e., higher proportion of red blood cells and higher vascular density), more robust removal of end-products, and anaerobic energy production. In accordance with previous findings, they observed increased oxygen carrying capacity (increased hematocrit, capillary density, and tissue oxygen content) in the experimental animals that had been acclimated to hypoxic conditions. Notably, the animals that had been acclimated showed over 50% reduction in the extent of a lesion caused by the experimentally induced stroke, showed reduced inflammatory response, and less severe behaviorally measured dysfunction than control animals.

The authors suggest that increased oxygen levels and increased capillary density explain the beneficial effects of hypoxia acclimation, and point to possibilities for development of targeted treatments (that increase stroke-resistance via similar mechanisms as hypoxia acclimation) especially for high-risk patients such as those who have already suffered a transient ischemic attack which is a severe warning signal. These results are highly interesting and pave way for clinical research on additional measures to reduce the devastating consequences of stroke.

Reference: Dunn JF, Wu Y, Zhao Z, Srinivasan S, Natah SS. Training the brain to survive stroke. PLoS ONE (2012) 7: e45108. http://dx.doi.org/10.1371/journal.pone.0045108

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