The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway.
The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway.
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选择性 mGluR5 激动剂 CHPG 通过 ERK 和 Akt 途径在体外和体内预防创伤性脑损伤
DOI：
10.3892/ijmm.2011.870
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
Fei Z
中科院分区：
文献类型：
--
作者：
Chen T;Zhang L;Qu Y;Huo K;Jiang X;Fei Z
I组代谢型谷氨酸受体（mGluRs）与中枢神经系统损伤的病理生理学有关，但mGluR 5在创伤性脑损伤（TBI）中的作用仍不清楚。在本研究中，我们研究了（R，S）-2-氯-5-羟基苯甘氨酸（CHPG），一种选择性mGluR 5激动剂，在体外和体内模型中对TBI的神经保护效力。在TBI之前30分钟，在体外制备中用ImM CHPG处理原代皮层神经元，并且在体内研究中在诱导TBI之前30分钟将250 nM CHPG注射到大鼠的右侧脑室中。结果表明，CHPG可明显减少乳酸脱氢酶（LDH）的释放和神经细胞凋亡，并缩小损伤体积。与对照组或载体组相比，细胞外信号调节激酶（ERK）和Akt的磷酸化水平在CHPG存在下增加，甚至在TBI诱导后也是如此。此外，用ERK抑制剂PD 98059或Akt抑制剂LY 294002处理部分逆转CHPG的神经保护作用。这些数据表明，CHPG在体外和体内诱导TBI后使脑损伤最小化，并且这些保护作用可能通过ERK和Akt信号通路的激活介导。因此，用选择性激动剂如CHPG增强mGluR 5活性可用于治疗创伤性脑损伤。
Group I metabotropic glutamate receptors (mGluRs) have been implicated in the pathophysiology of central nervous system injury, but the role of mGluR5 in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the neuroprotective potency of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), a selective mGluR5 agonist, for protecting against TBI in both in vitro and in vivo models. Primary cortical neurons were treated with 1 mM CHPG in an in vitro preparation 30 min before TBI, and 250 nM CHPG was injected into the right lateral ventricle of rats 30 min before TBI was induced in in vivo studies. The results showed that CHPG significantly attenuated lactate dehydrogenase (LDH) release and neuronal apoptosis and reduced lesion volume. Compared to the control or vehicle group, the phosphorylation levels of extracellular signal-regulated kinase (ERK) and Akt were increased in the presence of CHPG, even following the induction of TBI. Furthermore, treatment with either the ERK inhibitor PD98059 or Akt inhibitor LY294002 partially reversed the CHPG's neuroprotective effects. These data suggest that CHPG minimizes brain damage after induction of TBI both in vitro and in vivo, and that these protective effects were possibly mediated by activation of the ERK and Akt signaling pathways. Thus, potentiating mGluR5 activity with selective agonists such as CHPG may be useful for the treatment of traumatic brain injury.
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影响因子：
4.2
作者：
Belayev, L;Alonso, OF;Busto, R
通讯作者：
Busto, R
影响因子：
3.4
作者：
Copani, A;Casabona, G;Nicoletti, F
通讯作者：
Nicoletti, F
影响因子：
4.1
作者：
Bullock, R;Zauner, A;Young, HF
通讯作者：
Young, HF
影响因子：
3.4
作者：
Atkins, Coleen M.;Oliva, Anthony A., Jr.;Dietrich, W. Dalton
通讯作者：
Dietrich, W. Dalton
影响因子：
5.3
作者：
Faden, AI;O'Leary, DM;Movsesyan, VA
通讯作者：
Movsesyan, VA