A model of traumatic brain injury in rats is influenced by neuroprotection of diurnal variation which improves motor behavior and histopathology in white matter myelin.

Traumatic brain injury (TBI) represents a significant public health concern and has been associated with high rates of morbidity and mortality. TBI generates two types of brain damage: primary and secondary. Secondary damage originates a series of pathophysiological processes, which include metabolic crisis, excitotoxicity, and neuroinflammation, which have deleterious consequences for neuronal function. However, neuroprotective mechanisms are also activated. The balance among these tissue responses, and its variations throughout the day determines the fate of the damage tissue. We have demonstrated less behavioral and morphological damage when a rat model of TBI was induced during the light hours of the day. Moreover, here we show that rats subjected to TBI in the dark lost less body weight than those subjected to TBI in the light, despite no change in food intake. Besides, the rats subjected to TBI in the dark had better performance in the beam walking test and presented less histological damage in the corpus callosum and the cingulum bundle, as shown by the Klüver-Barrera staining. Our results suggest that the time of day when the injury occurs is important. Thus, this data should be used to evaluate the pathophysiological processes of TBI events and develop better therapies.

On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.

Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 µM) were tested in cerebellum and forebrain homogenates exposed to 5 µM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 µM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 µM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 µM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 µM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.