How to boost the effects of exercise to favor traumatic brain injury outcome

Abstract

Physical rehabilitation is an effective therapy to normalize weaknesses encountered with neurological disorders such as traumatic brain injury (TBI). However, the efficacy of exercise is limited during the acute period of TBI because of metabolic dysfunction, and this may further compromise neuronal function. Here we discuss the possibility to normalize brain metabolism during the early post-injury convalescence period to support functional plasticity and prevent long-term functional deficits. Although BDNF possesses the unique ability to support molecular events involved with the transmission of information across nerve cells through activation of its TrkB receptor, the poor pharmacokinetic profile of BDNF has limited its therapeutic applicability. The flavonoid derivative, 7,8-dihydroxyflavone (7,8-DHF), signals through the same TrkB receptors and results in the activation of BDNF signaling pathways. We discuss how the pharmacokinetic limitations of BDNF may be avoided by the use of 7,8-DHF, which makes it a promising pharmacological agent for supporting activity-based rehabilitation during the acute post-injury period after TBI. In turn, docosahexaenoic acid (C22:6n-3; DHA) is abundant in the phospholipid composition of plasma membranes in the brain and its action is important for brain development and plasticity. DHA is a major modulator of synaptic membrane fluidity and function, which is fundamental for supporting cell signaling and synaptic plasticity. Exercise influences DHA function by normalizing DHA content in the brain, such that the collaborative action of exercise and DHA can be instrumental to boost BDNF function with strong therapeutic potential for reducing the deleterious effects of TBI on synaptic plasticity and cognition.

Keywords

• Exercise
• Traumatic brain injury
• Brain
• Synaptic plasticity
• DHA
• BDNF