A novel model of blast induced traumatic brain injury caused by compressed gas produced sustained cognitive deficits in rats: involvement of phosphorylation of tau at the Thr205 epitope.
Brain Res Bull
; 157: 149-161, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-32044361
ABSTRACT
Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24â¯-h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24â¯-h mortality using peak overpressure fits with the following areas under ROC curves 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20â¯cm distance from the blast (about 136.44â¯kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20â¯cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12â¯h, 24â¯h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12â¯h after blast injury and significantly increased IL-6 production at 12â¯h, 24â¯h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24â¯h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transtornos Cognitivos
/
Disfunção Cognitiva
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Lesões Encefálicas Traumáticas
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Epitopos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res Bull
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China