Background: Presently, little can be done to repair brain tissue after stroke damage. We hypothesized that the mammalian
brain has an intrinsic capacity to adapt to low oxygen which would improve outcome from a reversible hypoxic/ischemic
episode. Acclimation to chronic hypoxia causes increased capillarity and tissue oxygen levels which may improve the
capacity to survive ischemia. Identification of these adaptations will lead to protocols which high risk groups could use to
improve recovery and reduce costs.
Methods and Findings: Rats were exposed to hypoxia (3 weeks living at K an atmosphere). After acclimation, capillary
density was measured morphometrically and was increased by 30% in the cortex. Novel implantable oxygen sensors
showed that partial pressure of oxygen in the brain was increased by 40% in the normal cortex. Infarcts were induced in
brain with 1 h reversible middle cerebral artery occlusions. After ischemia (48 h) behavioural scores were improved and T2
weighted MRI lesion volumes were reduced by 52% in acclimated groups. There was a reduction in inflammation indicated
by reduced lymphocytes (by 27–33%), and ED1 positive cells (by 35–45%).
Conclusions: It is possible to stimulate a natural adaptive mechanism in the brain which will reduce damage and improve
outcome for a given ischemic event. Since these adaptations occur after factors such as HIF-1a have returned to baseline,
protection is likely related more to morphological changes such as angiogenesis. Such pre-conditioning, perhaps with
exercise or pharmaceuticals, would not necessarily reduce the incidence of stroke, but the severity of damage could be
reduced by 50%.
National Institutes of Health; Canadian Institutes of Health Research; the Canadian Foundation for Innovation ; the Alberta Heritage Foundation and the Canadian National Sciences and Engineering Research Council