Mini-Reviews in Medicinal Chemistry, MRMC 16-1

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Creatine supplementation and physical exercise: role on traumatic brain injury

Prof. Luiz Fernando Freire Royes, Mr. Gustavo Cassol


Traumatic brain Injury (TBI) is a devastating disease frequently followed by significant behavioral disabilities and long-term medical complications that include a wide range of behavioral and emotional problems. The present condition is characterized by a combination of immediate mechanical dysfunction of brain tissue and secondary damage developed over a period of hours to days following injury. The early inflammatory response after tissue injury is believed to be triggered from several factors, such as extravasated blood products and reactive species generation (ROS). It is important to note that energy generation and mitochondrial function are closely related to and interconnected with other delayed secondary manifestations of injury, including early neuromotor dysfunction, cognitive impairment and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibilities of rapid amplification of secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being actively studied. In this context, the present review covers the preclinical and clinical literature supporting the role of inflammatory and free radical in the secondary damage in several models of TBI. Furthermore, the present review aims to discuss the role of Creatine, a guanidine compound popularized as a performance-enhancing supplement used to increase high-intensity athletic performance on secondary damage induced by TBI. In this narrative review, we also discuss the beneficial effect of exercise performed in animal models of TBI and how the results from animal’s studies can be used in clinical settings.


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