The immunological influence of physical exercise on TBI-induced pathophysiology: Crosstalk between the spleen, gut, and brain.

Traumatic brain injury (TBI) is a non-degenerative and non-congenital insult to the brain and is recognized as a global public health problem, with a high incidence of neurological disorders. Despite the causal relationship not being entirely known, it has been suggested that multiorgan inflammatory response involving the autonomic nervous system and the spleen-gut brain axis dysfunction exacerbate the TBI pathogenesis in the brain. Thus, applying new therapeutic tools, such as physical exercise, have been described in the literature to act on the immune modulation induced by brain injuries. However, there are caveats to consider when interpreting the effects of physical exercise on this neurological injury. Given the above, this review will highlight the main findings of the literature involving peripheral immune responses in TBI-induced neurological damage and how changes in the cellular metabolism of the spleen-gut brain axis elicited by different protocols of physical exercise alter the pathophysiology induced by this neurological injury.

Aflatoxin B1 reduces non-enzymatic antioxidant defenses and increases protein kinase C activation in the cerebral cortex of young rats.

OBJECTIVES: Aflatoxin B1 (AFB1) is the most widespread mycotoxin, and it is a feed contaminant and is highly toxic, causing carcinogenic, mutagenic, and teratogenic effects. Many researches clarified the peripheral effects of the exposition to AFB1; however, there are few studies explaining their effects on central nervous system. The aim of the present study was to evaluate the effects caused by acute oral administration of AFB1 on behavioral tests and selected biochemical parameters. METHODS: Young male Wistar rats received a single administration of AFB1 (250 µg/kg/i.g.) and 48 hours thereafter they were subjected to behavioral analysis. After the tests, biochemical parameters were measured in the cerebral cortex. RESULTS: Acute treatment with AFB1 caused neurotoxic effects, evidenced by a significant reduction in the levels of non-enzymatic antioxidant defenses, ascorbic acid, and non-protein sulfhydryl groups. In addition, AFB1 increased protein kinase C (PKC) activation, evidenced by an increase in phosphorylation of Ser957 of PKCα. DISCUSSION: In this acute protocol, a single oral administration of AFB1 was able to cause changes in important neurochemical parameters, without concomitant, detectable behavioral alterations. These results reinforce that monitoring mycotoxin levels in food is essential to guarantee food security.

Regulation of Mitochondrial Function and Glutamatergic System Are the Target of Guanosine Effect in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca2+ homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.