This is the fourth and final post is a series focusing on exercise and the brain. In the first post, I reviewed research documenting the brain's role in exercise fatigue. The second post examined the hypothesis that aerobic physical activity had a key evolutionary role in the growth of brain size in humans. The third post focused on animal study research supporting a role for exercise in reducing vulnerability to anxiety by changes in the 5-HT2C serotonin receptor.
In this post, I will review a provocative study suggesting that physical fitness and it's effect on brain vascular health, may limit the brain damage produced by stroke.
Dunn and colleagues at the University of Calgary in Canada conducted an experiment in rats that has recently been published in the journal PLOS ONE. They noted that in the mammalian brain a chemical called hypoxia inducible factor, or HIF-1alpha, exists that improves "the capacity of tissue to survive low oxygen conditions". They hypothesized that manipulation of environmental factors that increase HIF-1alpha may serve as a potential mechanism to reduce the brain damage associated with hypoxic events.
In their study, rather than exercise, they exposed rats to hypoxia by placing them in a 1/2 atmosphere environment for three weeks. This results in brain changes that can also be seen with aerobic exercise including:- Increase in capillary density by up to 30%
- Increase in brain oxygen partial pressure by up to 40%
The hypoxia-exposed experimental rat group was then compared to a group of control rats following stroke simulation by occlusion of the middle cerebral artery for one hour. They then compared the stroke outcome of the case and control groups and noted the following key findings:
- Case rats had an increase in total hemoglobin, total hematocrit, capillary density and brain tissue oxygen level prior to the stroke simulation
- Absolute brain volume of stroke damage assessed by magnetic resonance imaging was reduced by 52% in the case group compared to controls
- Case rats showed no motor behavioral deficits 48 hours after the stroke simulation while control rats showed continued motor deficits
- Case rats showed a reduction in brain inflammation post stroke simulation measured by levels of lymphocyte infiltration and number of macrophages
The authors note in their discussion, that one clinical implication from their study relates to humans living in high altitudes under chronic acclimation to hypoxia. They note there is limited study of stroke in these populations. There is some human research showing that chronic high-altitude hypoxia with increased hemoglobin and hematocrit might actually lead to a higher incidence of stroke. However, individuals living at high-altitude might be expected to have a better stroke outcome due to other adaptive brain mechanisms associated with acclimation to hypoxia.
The authors also note their study supports additional research in humans for ways to increase brain neuroplasticity through stimulation of HIF-1alpha. This might be accomplished by a high baseline rate of aerobic exercise or use of pharmacological agents such as desferoxamine.
Such interventions in high-risk stroke populations (i.e. those who have had a transient ischemic attack) may lead to reduction in brain damage related to future stroke events.
For the general population, this study suggests one benefit of aerobic exercise might include reduction in both the risk for stroke and a better outcome if one occurs.
For free access to this study, select the PMID link from the reference below.
Photo of blue jay is from the author's files.
Dunn JF, Wu Y, Zhao Z, Srinivasan S, & Natah SS (2012). Training the brain to survive stroke. PloS one, 7 (9) PMID: 23028788
