Physical Exercise as a Modulator of Vascular Pathology and Thrombin Generation to Improve Outcomes After Traumatic Brain Injury.

Disruption of the blood-brain barrier and occurrence of coagulopathy after traumatic brain injury (TBI) have important implications for multiple secondary injury processes. Given the extent of post-traumatic changes in neuronal function, significant alterations in some targets, such thrombin (a protease that plays a physiological role in maintaining blood coagulation), play an important role in TBI-induced pathophysiology. Despite the magnitude of thrombin in synaptic plasticity being concentration-dependent, the mechanisms underlying TBI have not been fully elucidated. The understanding of this post-injury neurovascular dysregulation is essential to establish scientific-based rehabilitative strategies. One of these strategies may be supporting physical exercise, considering its relevance in reducing damage after a TBI. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI. To complete this picture, this review will describe how the interactions established between blood-borne factors (such as thrombin) and physical exercise alter the TBI pathophysiology.

Modulation of Na+/K+- ATPase activity by triterpene 3ß, 6ß, 16ß-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a public health problem characterized by a combination of immediate mechanical dysfunction of the brain tissue, and secondary damage. Based on the hypothesis that selected targets, such as Na+ K+-ATPase are involved in the secondary damage after TBI and modulation of this enzyme activity by triterpene 3ß, 6ß, 16ß-trihidroxilup-20 (29)-ene (TTHL) supports the ethnomedical applications of this plant, we decided to investigate whether previous TTHL treatment interrupts the progression of pathophysiology induced by TBI. Statistical analyses revealed that percussion fluid injury (FPI) increased Na+,K+-ATPase activity in all isoform (α1 and α2/3) 15 min after neuronal injury. The FPI protocol inhibited Na+,K+-ATPase activity total and α1 isoform, increased [3H]MK-801 binding but did not alter Dichloro-dihydro-fluorescein diacetate (DCFH-DA) oxidation, carbonylated proteins and free -SH groups 60 min after injury. The increase of immunoreactivity of protein PKC and state of phosphorylation of at Ser16 of Na+,K+-ATPase 60 min after FPI suggest the involvement of PKC on Na+,K+-ATPase activity oscillations characterized by inhibition of total and α1 isoform. Our experimental data also revealed that natural product rich in compounds such as triterpenes (TTHL; 30 mg/kg) attenuates [3H]MK-801 binding increase, phosphorylation of the PKC and the Na+,K+-ATPase alpha 1 subunit (Ser16) induced by FPI. The previous TTHL treatment had not effect on motor disability but protected against spatial memory deficit, BDNF, TrKB expression decrease, protein carbonylation and hippocampal cell death 7 days after FPI. These data suggest that TTHL-induced reduction on initial damage limits the long-term secondary degeneration and supports neural repair or behavioral compensation after neuronal injury.