(+)-Naltrexone is neuroprotective and promotes alternative activation in the mouse hippocampus after cardiac arrest/cardiopulmonary resuscitation.
(+)-Naltrexone is neuroprotective and promotes alternative activation in the mouse hippocampus after cardiac arrest/cardiopulmonary resuscitation.
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DOI：
10.1016/j.bbi.2015.03.005
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Herson PS
中科院分区：
文献类型：
--
作者：
Grace PM;Shimizu K;Strand KA;Rice KC;Deng G;Watkins LR;Herson PS
尽管心肺复苏术（CPR）和其他心脏骤停（CA）技术有了显着改善，但大多数幸存者继续表现出记忆或执行认知功能下降的迹象。这种记忆障碍可能是由于海马CA 1区神经元死亡，这是由CA/CPR后几天延迟。CA 1区的典型小胶质细胞增生可能导致神经元死亡，但关键活化受体Toll样受体4（TLR 4）的作用尚未在CA/CPR后研究。我们表明，（+）-纳洛酮是CA/CPR后的神经保护。TLR 4阻断与小胶质细胞/巨噬细胞活化和T细胞和B细胞浸润的标志物的表达降低以及促炎细胞因子水平降低相关。值得注意的是，IL-10的表达升高，响应CA/CPR，但不衰减（+）-纳洛酮，表明当地的单核细胞/小胶质细胞表型已转向替代激活。精氨酸酶-1的表达升高，NFκB B p65亚基的表达降低证实了这一点。因此，（+）-纳洛酮和其他TLR 4拮抗剂可能代表一种新的治疗策略，以减轻CA/CPR后的记忆或执行认知功能障碍的实质性负担。
Despite dramatic improvement in cardiopulmonary resuscitation (CPR) and other techniques for cardiac arrest (CA), the majority of survivors continue to show signs of decreased memory or executive cognitive function. Such memory impairment may be due to hippocampal CA1 neuronal death, which is delayed by several days after CA/CPR. Classical microgliosis in the CA1 region may contribute to neuronal death, yet the role of a key activation receptor Toll Like Receptor 4 (TLR4) has not been previously investigated for such neuronal death after CA/CPR. We show that (+)-naltrexone was neuroprotective after CA/CPR. TLR4 blockade was associated with decreased expression of markers for microglial/macrophage activation and T cell and B cell infiltration, as well as decreased pro-inflammatory cytokine levels. Notably, IL-10 expression was elevated in response to CA/CPR, but was not attenuated by (+)-naltrexone, suggesting that the local monocyte/microglial phenotype had shifted towards alternative activation. This was confirmed by elevated expression of Arginase-1, and decreased expression of NFκB p65 subunit. Thus, (+)-naltrexone and other TLR4 antagonists may represent a novel therapeutic strategy to alleviate the substantial burden of memory or executive cognitive function impairment after CA/CPR.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
3
作者：
Kofler, J;Hattori, K;Traystman, RJ
通讯作者：
Traystman, RJ
影响因子：
3.3
作者：
Deng, Guiying;Carter, Jessica;Herson, Paco S.
通讯作者：
Herson, Paco S.
影响因子：
3.3
作者：
Quillinan, N.;Grewal, H.;Deng, G.;Shimizu, K.;Yonchek, J. C.;Strnad, F.;Traystman, R. J.;Herson, P. S.
通讯作者：
Herson, P. S.
影响因子：
10.5
作者：
Takeda, Norihiko;O'Dea, Ellen L.;Johnson, Randall S.
通讯作者：
Johnson, Randall S.