Cognitive Deficits and Inflammatory Response Resulting from Mild-to-Moderate Traumatic Brain Injury in Rats Are Exacerbated by Repeated Pre-Exposure to an Innate Stress Stimulus

Abstract

Traumatic brain injury (TBI) is common in both military and civilian populations, and often results in neurobehavioral sequelae that impair quality of life in both patients and their families. Although individuals who are chronically exposed to stress are more likely to experience TBI, it is still unknown whether pre-injury stress influences the outcome after TBI. The present study tested whether behavioral and cognitive long-term outcome after TBI in rats is affected by prior exposure to an innate stress stimulus. Young adult male Sprague-Dawley rats were exposed to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) or to water (WAT); exposure was repeated eight times at irregular intervals over a 2-week period. Rats were subsequently subjected to either mild-to-moderate bilateral brain injury (lateral fluid percussion [LFP]) or sham surgery (Sham). Four experimental groups were studied: Sham-WAT, Sham-TMT, LFP-WAT and LFP-TMT. Compared with Sham-WAT rats, LFP-WAT rats exhibited transient locomotor hyperactivity without signs of anxiety, minor spatial learning acquisition and hippocampal long-term potentiation deficits, and lower baseline activity of the hypothalamic-pituitary-adrenal axis with slightly stronger reactivity to restraint stress. Exposure to TMT had only negligible effects on Sham rats, whereas it exacerbated all deficits in LFP rats except for locomotor hyperactivity. Early brain inflammatory response (8 h post-trauma) was aggravated in rats pre-exposed to TMT, suggesting that increased brain inflammation may sustain functional deficits in these rats. Hence, these data suggest that pre-exposure to stressful conditions can aggravate long-term deficits induced by TBI, leading to severe stress response deficits, possibly due to dysregulated inflammatory response.

DPP‐4 inhibitor reduces striatal microglial deramification after sensorimotor cortex injury induced by external force impact

“…Consistent with previous reports, 49‐54 we demonstrated an increased spontaneous locomotor activity following CCI. The hyperactivity may be attributed to the enhanced striatal dopaminergic transmission after selectively lesioning frontoparietal cortex and striatum 54‐57 .…”

In search of antiepileptogenic treatments for post-traumatic epilepsy

“…PTE may negatively affect the quality of life of affected individuals due to direct and indirect impact of epileptic seizures (e.g., seizure-induced injuries or medical issues) and epilepsy-related comorbidities (e.g., behavioral, cognitive or other medical) or consequences (e.g., medication adverse effects, impact on quality of life, mortality) (Piccenna et al, 2017). PTE may further exacerbate or add to the effects of TBI on memory and cognition (Luo et al, 2014;Muccigrosso et al, 2016;Ogier et al, 2017), cerebral vasculature or blood brain barrier injury (Golding et al, 1999), sleep disorders (Castriotta et al, 2007), depression and post-traumatic stress disorder (Vos et al, 2018).…”

Low grade inflammation in the epileptic hippocampus contrasts with explosive inflammation occurring in the acute phase followingstatus epilepticusin rats: translation to patients with epilepsy

“…Furthermore, PCR is quantitative as soon as it is performed on a real-time thermocycler and a calibration curve is used, giving access to the number of cDNA copies detected. To generate the cDNAs to be amplified by PCR, we have chosen a method that allows us to calibrate reverse transcription using a synthetic and exogenous poly-A RNA (SmRNA) (WO20040404092414) [13, 29, 30, 39]. This contrasts with the selection of one or more endogenous genes, so-called housekeeping genes, considered as internal controls and, de facto , as being a priori invariant in all studies that use this kind of standardization.…”