Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury.
Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury.
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DOI：
10.3389/fnbeh.2022.903980
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发表时间：
2022
影响因子：
3
通讯作者：
中科院分区：
文献类型：
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创伤性脑损伤 (TBI) 是美国致残的主要原因。血管紧张素 1-7 (Ang-1-7) 是一种内源性肽，作用于 G 蛋白偶联 MAS1 受体 (MASR)，抑制炎症介质并减少 CNS 内的活性氧。很少有研究确定 Ang-(1-7) 是否可以减轻闭合性 TBI 后的认知障碍。本研究检验了 Ang-(1-7) 对在封闭颅骨、单一损伤模型中的轻度 TBI (mTBI) 小鼠模型中观察到的继发性损伤的治疗效果。雄性小鼠 (n = 108) 接受了闭合颅骨、控制性皮质撞击损伤。受伤后两小时，给小鼠注射 Ang-(1-7) (n = 12) 或媒介物 (n = 12)，持续到 TBI 后第 5 天，并在第 1-5 天和第 18 天测试认知障碍。在多个时间点测量 pTau、Tau、GFAP 和血清细胞因子。每天通过新物体识别观察动物的认知和运动协调能力。对脑切片进行染色并评估神经元损伤。与盐水对照治疗的动物相比，mTBI 后连续 5 天每天施用 Ang-(1-7) 显着增强了认知功能。与对照组相比，Ang-(1-7) 存在时皮质和海马结构的损伤较小，而 Ang-(1-7) 给药显着改变了皮质和海马区域 pTau 和 GFAP 的表达。这些是首批证明在闭合颅骨、单次冲击 mTBI 后持续给予 Ang-(1-7) 的研究可显着改善神经系统结果，可能为预防此类损伤后的长期 CNS 损伤提供一种新的治疗方式。
Traumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model. Male mice (n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) (n = 12) or vehicle (n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1–5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury. Administration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control. These are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries.
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血管紧张素 - （1-7）/MAS受体作为癌症引起的骨痛的抗伤害感受剂。
影响因子：
7.4
作者：
Forte BL;Slosky LM;Zhang H;Arnold MR;Staatz WD;Hay M;Largent-Milnes TM;Vanderah TW
通讯作者：
Vanderah TW
DOI：
10.1097/htr.0b013e318289ede5
发表时间：
2014-03
期刊：
The Journal of head trauma rehabilitation
影响因子：
--
作者：
Arenth PM;Russell KC;Scanlon JM;Kessler LJ;Ricker JH
通讯作者：
Ricker JH
影响因子：
3.3
作者：
Rowe RK;Ellis GI;Harrison JL;Bachstetter AD;Corder GF;Van Eldik LJ;Taylor BK;Marti F;Lifshitz J
通讯作者：
Lifshitz J
DOI：
10.1073/pnas.1432869100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Santos, RAS;Silva, ACSE;Walther, T
通讯作者：
Walther, T
影响因子：
5.6
作者：
Frati A;Cerretani D;Fiaschi AI;Frati P;Gatto V;La Russa R;Pesce A;Pinchi E;Santurro A;Fraschetti F;Fineschi V
通讯作者：
Fineschi V