Persistent Infiltration and Impaired Response of Peripherally-Derived Monocytes after Traumatic Brain Injury in the Aged Brain.
Persistent Infiltration and Impaired Response of Peripherally-Derived Monocytes after Traumatic Brain Injury in the Aged Brain.
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DOI：
10.3390/ijms19061616
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发表时间：
2018-05-30
影响因子：
5.6
通讯作者：
Rosi S
中科院分区：
文献类型：
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作者：
Chou A;Krukowski K;Morganti JM;Riparip LK;Rosi S
外伤性脑损伤（TBI）是世界范围内神经系统残疾的主要原因。创伤性脑损伤最常见于老年人，老年创伤性脑损伤幸存者的恢复速度较慢，生活质量较差。年龄对创伤性脑损伤病理生理的影响尚不清楚。我们之前已经证实外周来源的单核细胞（CCR2+）浸润到受伤的大脑中，并在幼年动物中导致慢性tbi诱导的认知缺陷。此外，年龄对损伤后单核细胞浸润有明显的增强作用。在目前的研究中，我们研究了年龄对外周来源单核细胞（CD45hi; CCR2+）亚慢性反应的影响及其在慢性认知缺陷发展中的作用。在年老的大脑中，与年轻的受伤动物相比，损伤后外周来源的单核细胞数量显著增加。外周源性单核细胞的浸润率亚慢性升高，并与CCR2趋化配体的表达增强相对应。有趣的是，与年轻动物相比，在受伤的老年大脑中观察到的髓细胞群具有受损的抗炎反应。此外，在老年动物中，损伤后血液中CCR2+单核细胞数量增加，这在年轻动物中不存在。重要的是，敲除CCR2以抑制外周源性单核细胞的浸润可预防老年小鼠慢性tbi诱导的空间记忆缺陷。总之，这些结果表明，在TBI病理生理进展过程中，年龄对外周来源的单核细胞反应的关键影响。
Traumatic brain injury (TBI) is a leading cause for neurological disabilities world-wide. TBI occurs most frequently among the elderly population, and elderly TBI survivors suffer from reduced recovery and poorer quality of life. The effect of age on the pathophysiology of TBI is still poorly understood. We previously established that peripherally-derived monocytes (CCR2+) infiltrate the injured brain and contribute to chronic TBI-induced cognitive deficits in young animals. Furthermore, age was shown to amplify monocyte infiltration acutely after injury. In the current study, we investigated the impact of age on the subchronic response of peripherally-derived monocytes (CD45hi; CCR2+) and their role in the development of chronic cognitive deficits. In the aged brain, there was a significant increase in the number of peripherally-derived monocytes after injury compared to young, injured animals. The infiltration rate of peripherally-derived monocytes remained elevated subchronically and corresponded with enhanced expression of CCR2 chemotactic ligands. Interestingly, the myeloid cell populations observed in injured aged brains had impaired anti-inflammatory responses compared to those in young animals. Additionally, in the aged animals, there was an expansion of the blood CCR2+ monocyte population after injury that was not present in the young animals. Importantly, knocking out CCR2 to inhibit infiltration of peripherally-derived monocytes prevented chronic TBI-induced spatial memory deficits in the aged mice. Altogether, these results demonstrate the critical effects of age on the peripherally-derived monocyte response during the progression of TBI pathophysiology.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
8.2
作者：
Kawata, Keisuke;Liu, Charles Y.;Merkel, Steven F.;Ramirez, Servio H.;Tierney, Ryan T.;Langford, Dianne
通讯作者：
Langford, Dianne
影响因子：
4.2
作者：
Hsieh, Christine L.;Niemi, Erene C.;Nakamura, Mary C.
通讯作者：
Nakamura, Mary C.
影响因子：
4.2
作者：
Lee DC;Ruiz CR;Lebson L;Selenica ML;Rizer J;Hunt JB Jr;Rojiani R;Reid P;Kammath S;Nash K;Dickey CA;Gordon M;Morgan D
通讯作者：
Morgan D
影响因子：
16.6
作者：
通讯作者：
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