Dataset Information

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.

SUBMITTER: Martinez-Tapia RJ

PROVIDER: S-EPMC7550533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Martinez-Tapia Ricardo Jesus RJ Estrada-Rojo Francisco F Lopez-Aceves Teresita Guadalupe TG Rodríguez-Mata Veronica V Perez-Torres Armando A Barajas-Martinez Antonio A Garcia-Velasco Stephany S Ugalde-Muñiz Perla P Navarro Luz L

Frontiers in neuroscience 20200929

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 th ...[more]

PMID: 33132827

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Project description:The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans, while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters. In this study, we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences. The severe controlled cortical impact model was produced by an electronic controlled cortical impact device, while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube. Body temperature and mortality were recorded, and neurological deficits were assessed with the modified neurological severity score. Brain edema and blood-brain barrier damage were evaluated by assessing brain water content and Evans blue extravasation. In addition, a cytokine array kit was used to detect inflammatory cytokines. Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining. Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations. More severe motor dysfunction was observed in the severe controlled cortical impact model, while more severe cognitive dysfunction was observed in the severe free weight drop model. Brain edema, inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group. The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage, with higher mortality and lower repeatability compared with the severe controlled cortical impact group. Severe brainstem damage was not found in the severe controlled cortical impact model. These results indicate that the severe controlled cortical impact model is relatively more stable, more reproducible, and shows obvious cerebral pathological changes at an earlier stage. Therefore, the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury, while the severe free weight drop model may be more apt for studies on diffuse axonal injury. All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University, China (approval No. IRB2012-028-02) in February 2012.

Project description:BackgroundThe annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3-5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure. The purpose of this study was to determine the behavioural and neuropathological phenotypes induced by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model of mTBI in both wild-type (WT) and APP/PS1 mice up to 8?months post-injury.MethodsMale WT and APP/PS1 littermates were randomized to sham or repetitive mild TBI (rmTBI; 2?×?0.5?J impacts 24?h apart) groups at 5.7?months of age. Animals were assessed up to 8?months post-injury for acute neurological deficits using the loss of righting reflex (LRR) and Neurological Severity Score (NSS) tasks, and chronic behavioural changes using the passive avoidance (PA), Barnes maze (BM), elevated plus maze (EPM) and rotarod (RR) tasks. Neuropathological assessments included white matter damage; grey matter inflammation; and measures of A? levels, deposition, and aducanumab binding activity.ResultsThe very mild CHIMERA rmTBI conditions used here produced no significant acute neurological or motor deficits in WT and APP/PS1 mice, but they profoundly inhibited extinction of fear memory specifically in APP/PS1 mice over the 8-month assessment period. Spatial learning and memory were affected by both injury and genotype. Anxiety and risk-taking behaviour were affected by injury but not genotype. CHIMERA rmTBI induced chronic white matter microgliosis, axonal injury and astrogliosis independent of genotype in the optic tract but not the corpus callosum, and it altered microgliosis in APP/PS1 amygdala and hippocampus. Finally, rmTBI did not alter long-term tau, A? or amyloid levels, but it increased aducanumab binding activity.ConclusionsCHIMERA is a useful model to investigate the chronic consequences of rmTBI, including behavioural abnormalities consistent with features of post-traumatic stress disorder and inflammation of both white and grey matter. The presence of human A? greatly modified extinction of fear memory after rmTBI.

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Dataset Information

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

Publications

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

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