Diurnal Variation Induces Neurobehavioral and Neuropathological Differences in a Rat Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) induces two types of brain damage: primary and secondary. Damage initiates a series of pathophysiological processes, such as metabolic crisis, excitotoxicity with oxidative stress-induced damage, and neuroinflammation. The long-term perpetuation of these processes has deleterious consequences for neuronal function. However, it remains to be elucidated further whether physiological variation in the brain microenvironment, depending on diurnal variations, influences the damage, and consequently, exerts a neuroprotective effect. Here, we established an experimental rat model of TBI and evaluated the effects of TBI induced at two different time points of the light–dark cycle. Behavioral responses were assessed using a 21-point neurobehavioral scale and the cylinder test. Morphological damage was assessed in different regions of the central nervous system. We found that rats that experienced a TBI during the dark hours had better behavioral performance than those injured during the light hours. Differences in behavioral performance correlated with less morphological damage in the perilesional zone. Moreover, certain brain areas (CA1 and dentate gyrus subregions of the hippocampus) were less prone to damage in rats that experienced a TBI during the dark hours. Our results suggest that diurnal variation is a crucial determinant of TBI outcome, and the hour of the day at which an injury occurs should be considered for future research.

Circadian modulation of microglial physiological processes and immune responses

“…A clear example can be observed in a study by Martinez‐Tapia et al that demonstrated that the outcome of a traumatic brain injury (TBI) differs depending on the moment of the light–dark cycle in which the injury occurs. In this study, the rats subjected to a TBI protocol at midnight had better behavioral outcome than those subjected during the light phase (Martinez‐Tapia et al, 2020 ). Coincidentally the moment of the worst behavioral outcome coincides with the time of the day in which microglia has the highest levels of pro‐inflammatory cytokines in the cortex (Ni et al, 2019 ).…”

Octreotide-mediated neurofunctional recovery in rats following traumatic brain injury. Role of H2S, Nrf2 and TNF-α

“…Thereafter, the animals were allowed to recover. In sham, all procedures were performed, except inducing injury 21 .…”

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

“…30,31 Two other studies found greater neurological deficits and cell damage after TBI induced during the early or middle of subjective day vs. mid-to late subjective night. 32,33 Conversely, more cell death was observed in the hippocampus in response to nighttime compared to daytime ischemia. 34 The differences across these studies could be due to a variety of methodological factors, including differences in brain regions, methods of trauma, and how damage was assessed.…”