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Blocking B7-1/CD28 Pathway Diminished Long-Range Brain Damage by Regulating the Immune and Inflammatory Responses in a Mouse Model of Intracerebral Hemorrhage

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Abstract

Acute brain injuries can activate bidirectional crosstalk between the injured brain and the immune system. The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) binding cognate receptor provides a secondary signaling to T cell activation. The aim of our study was to explore the effects of anti-B7-1 antibody on the development and prognosis of cerebral hemorrhage and to investigate the possible underlying mechanism. Mice were inner canthus veniplex administered with anti-B7-1 antibody at 10 min and 24 h after ICH and sacrificed on the third day after ICH. Immune function was assessed via splenocyte proliferation assay and organism index, respectively. IFN-γ and IL-4 were detected by enzyme-linked immuno sorbent assay. The cerebral edema was evaluated via brain water content. The levels of autophagy and apoptosis related proteins were measured by western blotting analysis. In addition, functional outcome was studied with pole-climbing test and morris water maze. The mice were weighed on 0, 1, 3, 14 and 21 days after ICH. The treatment with anti-B7-1 antibody significantly lowered immune function, and reduced the latency of water maze on 18 and 20 days, the ratio of IFN-γ/IL-4 as well as body weight on day 3 after cerebral hemorrhage. Our study suggests that in the cerebral hemorrhage mice brain anti-B7-1 antibody may reduce long-range brain damage by reversing immune imbalance.

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Abbreviations

ICH:

Intracerebral hemorrhage

ELISA:

Enzyme-linked immuno sorbent assay

BBB:

Blood–brain barrier

APC:

Antigen presenting cells

TCR:

T cell receptor

MHC:

Major histocompatibility complex

SI:

Spleen index

TI:

Thymus index

IFN-γ:

Interferon-γ

IL-4:

Interleukin-4

LC3:

Microtubule-associated protein-1A/1B light chain 3

CNS:

Central nervous system

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Acknowledgments

We would like to thank Prof. Yuhua Qiu and her team for their helpful providing the anti-B7-1 antibody which comes from Department of Immunology in Soochow University. This work was supported by the National Natural Science Foundation of China (Nos. 81530062, 81271379, 81301039, 81373251 and 81400999), National High Technology Research and Development Program of China (863 Program, No. 2015AA020503), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    Authors and Affiliations

    1. Department of Forensic Medicine, Medical School of Soochow University, No. 178, Ganjiang East Road, Soochow, 215123, China

      Lu Ma, Xi Shen, Yuan Gao, Qiong Wu, Mengmeng Ji, Chengliang Luo, Mingyang Zhang, Tao Wang, Xiping Chen & Luyang Tao

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    Lu Ma and Xi Shen have contributed equally to the work.

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    Ma, L., Shen, X., Gao, Y. et al. Blocking B7-1/CD28 Pathway Diminished Long-Range Brain Damage by Regulating the Immune and Inflammatory Responses in a Mouse Model of Intracerebral Hemorrhage. Neurochem Res 41, 1673–1683 (2016). https://doi.org/10.1007/s11064-016-1883-3

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