Delayed Administration of an Angiotensin II Type 2 Receptor Agonist Promotes Functional Recovery of the Brain and Heart After Traumatic Brain Injury.
Yu QianShiying DongMeng NieYu TianMingqi LiuXuanhui LiuWeiwei JiangJiangyuan YuanChuang GaoPing LeiRongcai JiangPublished in: Journal of neurotrauma (2024)
Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.
Keyphrases
- traumatic brain injury
- angiotensin ii
- left ventricular
- severe traumatic brain injury
- blood brain barrier
- high glucose
- blood pressure
- diabetic rats
- heart failure
- resting state
- ejection fraction
- mild traumatic brain injury
- cerebral ischemia
- white matter
- poor prognosis
- angiotensin converting enzyme
- vascular smooth muscle cells
- cerebral blood flow
- functional connectivity
- atrial fibrillation
- acute myocardial infarction
- metabolic syndrome
- coronary artery disease
- type diabetes
- long non coding rna
- brain injury
- hypertensive patients
- blood glucose
- childhood cancer