O papel profilático do exercício físico sobre a modulação neurovascular e os efeitos da trombina no desenvolvimento de convulsões pós-traumáticas

Abstract

Traumatic brain injury (TBI) is considered a worldwide public health problem due to its high incidence and high public costs. Although the pathophysiology of TBI is multifaceted, the occurrence of coagulopathy is strongly associated with poor outcomes. Changes in the neurovascular tissue after trauma, increase the permeability of the blood-brain barrier (BBB), allowing the passage of proteases from the circulatory system, such as thrombin, to the brain parenchyma. In the brain, the presence of this protease promotes the activation of pro-inflammatory pathways and neuronal excitability through PAR-1 receptors, which may facilitate the appearance of post-traumatic seizures. In this sense, it is important to elucidate the exercise of physical exercise in protection against the development of post traumatic epilepsy and its relationship with the neurovascular system. Since exercise can positively influence the extracellular microenvironment and may promote neural repair processes, it is important to elucidate the involvement of physical activity in protecting against the development of epileptic seizures after TBI and its relationship with the neurovascular system. Along these lines, this paper presents a literature review regarding the effects of physical exercise on the neurovascular system after TBI. Furthermore, the effect of severe TBI induced by fluid percussion injury in Wistar rats was investigated, which were analyzed through an electroencephalographic (EEG) analysis via radio telemetry and subsequent biochemical analyses. The animals in the TBI group reinforced a significant increase in the number of spikes and in the frequency of waves in the electroencephalographic recordings, as well as decreasing the latency for the onset of the first crisis and increasing the mean duration of the seizures. Regarding biochemical analysis, an increase in thrombin and PAR-1 expression was observed in the hippocampus of animals 6 hours after TBI, as well as an increase in inflammatory markers, such as IL-1β and TNF-α. In addition, TBI induced an increase in protein expression p / t-AKT, p / t-P70, ERK 1/2 and GFAP. Additionally, animals that were discovered by TBI dissipated a reduction in the expression of Na +, K + -ATPase (NKA). Activation of inflammatory pathways and thrombin increased the animals brain excitability, contributing to the development of seizures.