Exercise preconditioning ameliorates inflammatory injury in ischemic rats during reperfusion

Abstract

There is evidence that physical activity is associated with decreased brain injury resulting from transient middle cerebral artery (MCA) occlusion. We investigated whether exercise could reduce stroke-induced brain inflammatory injury and its associated mediators. Sprague Dawley rats (3 months old) were subjected to 30 min exercise on a treadmill each day for 1-3 weeks. Stroke, in exercised and non-exercised animals, was then induced by a 2-h MCA occlusion followed by 48 h of reperfusion using an intraluminal filament. Endothelial expression of the intercellular adhesion molecule 1 (ICAM-1) and leukocyte infiltration were determined by immunocytochemistry. Expressions of tumor necrosis factor-alpha (TNF-alpha) and ICAM-1 mRNA were detected using a real-time reverse transcriptase-polymerase chain reaction in ischemic rats with or without exercise, and in non-ischemic control rats following exercise. Expression of TNF-alpha increased after exercise for 2 and 3 weeks. The overexpression of TNF-alpha was not further elevated in 3-week exercised rats subjected to a transient MCA occlusion and 6 or 12 h of reperfusion, as compared to that in non-exercised rats. Furthermore, ICAM-1 mRNA expression remained at significantly (P<0.01) low levels in exercised animals during ischemia/reperfusion. Pre-ischemic exercise significantly (P<0.01) reduced numbers of ICAM-1-positive vessels and infiltrating leukocytes in the frontoparietal cortex and dorsolateral striatum in ischemic rats after 48 h of reperfusion. Exercised ischemic rats demonstrated an 11+/-7% infarct volume of contralateral hemisphere as compared to a 52+/-3% volume in non-exercised ischemic rats. The data suggests that exercise inhibits inflammatory injury (i.e., decreased expression of inflammatory mediators and reduced accumulation of leukocytes) during reperfusion, leading to reduced brain damage. Chronically increased expression of TNF-alpha during exercise prevent the same downstream inflammatory events as does acutely elevated TNF-alpha after ischemia/reperfusion.

Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

“…In addition, regular exercise training-associated adaptation is a precondition against treatment with H 2 O 2 , which causes a significant degree of damage for untrained subjects (317). Moreover, when heart attacks or strokes are simulated in untrained and trained animals, the infarct size is significantly smaller in the trained groups (39,81), showing that regular exercise acts as a preconditioning tool (317) by enhancing the adaptive zone, by narrowing the theoretical distance between functional and biological endpoints. A great deal of evidence exists that suggests that regular exercise-induced adaptations to ROS handling, through redox signaling, including antioxidant and oxidative damage repair systems, significantly contribute to the health-promoting effects of regular exercise.…”

Biological mechanisms underlying the role of physical fitness in health and resilience

“…Regular exercise has also been shown to reduce brain inflammation in response to immune challenges, such as stroke [172] or peripheral infection [173]. And, as in the periphery, exercise-induced IL-6 production in the brain can exert an anti-inflammatory and protective role by inhibiting inflammatory TNFa signalling and attenuating neural cell death [174].…”

Whole Body Vibration Therapy after Ischemia Reduces Brain Damage in Reproductively Senescent Female Rats

“…Multiple studies using human and animal models have shown that preischemic physical activity reduces stroke impact on functional motor outcomes, edema, and infarct volume. The same studies also attributed these benefits to the mechanism of decreasing inflammation, and increasing brain-derived neurotrophic factor (BDNF) expression [2][3][4][5][6]. In many cases, however, stroke patients are unable to adhere to the physical activity regimen following their ischemic episodes due to a wide range of individual factors such as stroke severity, preexisting and comorbid conditions, motivation, fatigue, and depression.…”