A Sphingosine-1-Phosphate Receptor Modulator Attenuated Secondary Brain Injury and Improved Neurological Functions of Mice after ICH

被引：7
作者：
Bobinger, T. [1 ]
Baeuerle, T. [2 ]
Seyler, L. [2 ]
Horsten, S. [3 ,4 ]
Schwab, S. [1 ]
Huttner, H. B. [1 ]
Manaenko, A. [1 ]
机构：
[1] Friedrich Alexander Univ Erlangen Nurnberg, Dept Neurol, Erlangen, Germany
[2] Friedrich Alexander Univ Erlangen Nurnberg, Dept Radiol, Erlangen, Germany
[3] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Expt Therapy, Erlangen, Germany
[4] Friedrich Alexander Univ Erlangen Nurnberg, Preclin Expt Anim Ctr, Erlangen, Germany
来源：
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2020年 / 2020卷
关键词：
INTRACEREBRAL HEMORRHAGE; RAT MODEL; POSTHEMORRHAGIC HYDROCEPHALUS; EXPERIMENTAL STROKE; FINGOLIMOD; SIPONIMOD; DEFICITS; BARRIER; BETA;
D O I：
10.1155/2020/3214350
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Background. Stroke activates the immune system and induces brain infiltration by immune cells, aggravating brain injury. Poststroke immunomodulation via (S1P-)receptor modulation is beneficial; however, the S1P-modulator in clinical use (FTY-720) is unspecific, and undesirable side effects have been reported. Previously, we tested effects of a novel selective S1P-receptor modulator, Siponimod, on ICH-induced brain injury in acute stage of the disease. In the current study, we investigated whether protective effects of Siponimod, evaluated in a short-term study, will protect the brain of ICH animals at long term as well.Methods.134 C57BL/6N mice were divided into sham and ICH-operated groups. Collagenase model of ICH was employed. ICH animals were divided into Siponimod treated and nontreated. Dose- and time-dependent effects of Siponimod were investigated. Contraplay between development of brain injury and the number of lymphocytes infiltrating the brain was investigated by forelimb placing, T-Maze test, brain water content calculation, MRI scanning, and immunostaining.Results. Depending on the therapeutic strategy, Siponimod attenuated the development of brain edema, decreased ICH-induced ventriculomegaly and improved neurological functions of animals after ICH. It was associated with less lymphocytes in the brain of ICH animals.Conclusion. Siponimod is able to decrease the brain injury and improves neurological functions of animals after ICH.
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页数：8
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