Age-related CCL12 Aggravates Intracerebral Hemorrhage-induced Brain Injury via Recruitment of Macrophages and T Lymphocytes
| Autor: | Xiao-Yi Xiong, Guo-Qiang Yang, Yu Zhou, Lexing Xie, Ru Chen, Qingwu Yang, Junjie Yuan, Guo-Hui Jiang, Qi Xie, Qin Zhang, Wen-Jie Zi, Qiong Chen, Zhao-You Meng, Zhongming Qiu, Rui Xu, Maolin Wang, Jiacheng Huang, Chang-Xiong Gong |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Parabiosis Inflammation Immunofluorescence Orginal Article Pathology and Forensic Medicine Flow cytometry 03 medical and health sciences 0302 clinical medicine Internal medicine medicine CCL12 cardiovascular diseases Intracerebral hemorrhage medicine.diagnostic_test biology business.industry Cell Biology medicine.disease intracerebral hemorrhage nervous system diseases 030104 developmental biology Endocrinology age Apoptosis inflammation biology.protein Neurology (clinical) parabiosis Geriatrics and Gerontology Antibody medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Aging and Disease |
| ISSN: | 2152-5250 |
| Popis: | Circulating factors associated with aging have been shown to be involved in the development of age-related chronic and acute brain diseases. Here, we aimed to investigate the roles and mechanisms of CCL12, a circulating factor that is highly expressed in the plasma of aged rodents after intracerebral hemorrhage (ICH) using parabiosis and ICH models. Neurological deficit score (NDS), mortality rate, brain water content (BWC), and levels of inflammatory factors were determined to assess the degree of ICH-induced brain injury. Peripheral inflammatory cell infiltration was examined using immunofluorescence and flow cytometry. After confirming that acute brain injury after ICH was aggravated with age, we found that brain and plasma CCL12 levels were markedly higher in old mice than in young mice after ICH, and that plasma CCL12 was able to enter the brain. Using CCL12-/- mice, we showed that the degree of damage in the brain-as determined by NDS, mortality rate, BWC, levels of inflammatory factors, and numbers of degenerative and apoptotic neural cells and surviving neurons was significantly attenuated compared to that observed in old wild-type (WT) mice. These effects were reversed in CCL12-treated old mice. The detrimental effects caused by CCL12 may involve its ability to recruit macrophages and T cells. Finally, the administration of an anti-CCL12 antibody markedly improved the outcomes of ICH mice. Our results are the first to indicate that elevated peripheral CCL12 levels in old mice aggravates ICH-induced brain injury by recruiting macrophages and T cells. Thus, CCL12 may be a new target for ICH treatment. |
| Databáze: | OpenAIRE |
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