title: Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.
abstract: Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.
authors.affiliation: Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Zaorui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Boris
authors.initials: B
authors.lastname: Sabirzhanov
authors.affiliation: Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
authors.affiliation: Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Stoica
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000517:prevention & control / Q000628:therapy*; D004195:Disease Models, Animal; D005081:Exercise Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000066829:Neuroprotection / Q000502:physiology*; D010805:Physical Conditioning, Animal; D020127:Recovery of Function / Q000502:physiology*
keywords: controlled cortical impact; exercise; neuroprotection; traumatic brain injury