Novel humanized recombinant T cell receptor ligands protect the female brain after experimental stroke.
Novel humanized recombinant T cell receptor ligands protect the female brain after experimental stroke.
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DOI：
10.1007/s12975-014-0345-y
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发表时间：
2014-10
影响因子：
6.9
通讯作者：
Hurn, Patricia D.
中科院分区：
文献类型：
--
作者：
Pan, Jie;Palmateer, Julie;Schallert, Timothy;Hart, Madison;Pandya, Arushi;Vandenbark, Arthur A.;Offner, Halina;Hurn, Patricia D.
关键词：
外周血白细胞向脑的再迁移是脑缺血性细胞死亡机制的主要贡献者。人源化部分主要组织相容性复合物II类结构（pMHC），共价连接到髓鞘肽，是有效的治疗实验性中风的男性，但新的证据表明，一些炎性细胞死亡机制脑损伤后的性别特异性。我们在这里证明，pMHC结构的治疗也改善了大脑中动脉闭塞（MCAO）的雌性小鼠的结果。在再灌注后3、24、48和72小时，用RTL 1000（与人MOG-35-55肽连接的HLA-DR 2部分）、HLA-DRa 1-MOG-35-55或媒介物（VEH）处理患有MCAO的HLA-DR 2转基因雌性小鼠，并在损伤后96小时或2周恢复以测量组织学（TTC染色）或行为测试。与VEH组相比，RTL 1000和DRa 1-MOG处理的小鼠具有显著减少的梗死体积，尽管与先前评估的雄性相比，雌性需要更高剂量的DRa 1-MOG。RTL 1000处理的雌性动物在标准圆筒试验中也表现出明显改善的功能恢复。在缺血后超声发声（USV）的新研究中，通过动物对笼友的叫声来测量，我们在小鼠中模拟了人类中风幸存者中常见的中风后语言缺陷。无论RTL 1000治疗状态如何，相对于MCAO前基线，受伤动物的呼叫次数减少。然而，通过RTL 1000处理，呼叫持续时间显著改善，表明有益于动物的发声能力的恢复。我们的结论是，亲本RTL 1000分子和新的非多态性DRα1-MOG-35-55构建体都是治疗女性短暂性脑缺血的高效免疫疗法。
Transmigration of peripheral leukocytes to the brain is a major contributor to cerebral ischemic cell death mechanisms. Humanized partial major histocompatibility complex class II constructs (pMHC), covalently linked to myelin peptides, are effective for treating experimental stroke in males, but new evidence suggests that some inflammatory cell death mechanisms after brain injury are sex-specific. We here demonstrate that treatment with pMHC constructs also improves outcomes in female mice with middle cerebral artery occlusion (MCAO). HLA-DR2 transgenic female mice with MCAO were treated with RTL1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide), HLA-DRa1-MOG-35-55, or vehicle (VEH) at 3, 24, 48, and 72 h after reperfusion and were recovered for 96 h or 2 weeks post-injury for measurement of histology (TTC staining) or behavioral testing. RTL1000- and DRa1-MOG-treated mice had profoundly reduced infarct volumes as compared to the VEH group, although higher doses of DRa1-MOG were needed for females vs. males evaluated previously. RTL1000-treated females also exhibited strongly improved functional recovery in a standard cylinder test. In novel studies of post-ischemic ultrasonic vocalization (USV), as measured by animal calls to their cage mates, we modeled in mice the post-stroke speech deficits common in human stroke survivors. The number of calls was reduced in injured animals relative to pre-MCAO baseline regardless of RTL1000 treatment status. However, call duration was significantly improved by RTL1000 treatment, suggesting benefit to the animal’s recovery of vocalization capability. We conclude that both the parent RTL1000 molecule and the novel non-polymorphic DRα1-MOG-35-55 construct were highly effective immunotherapies for treatment of transient cerebral ischemia in females.
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DOI：
10.1111/j.1601-183x.2010.00570.x
发表时间：
2010-06-01
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Gaub S;Groszer M;Fisher SE;Ehret G
通讯作者：
Ehret G
影响因子：
5.3
作者：
Manwani, Bharti;Liu, Fudong;Scranton, Victoria;Hammond, Matthew D.;Sansing, Lauren H.;McCullough, Louise D.
通讯作者：
McCullough, Louise D.
DOI：
10.4049/jimmunol.1303118
发表时间：
2014-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Meza-Romero R;Benedek G;Yu X;Mooney JL;Dahan R;Duvshani N;Bucala R;Offner H;Reiter Y;Burrows GG;Vandenbark AA
通讯作者：
Vandenbark AA
影响因子：
3.6
作者：
Dziennis, Suzan;Mader, Sarah;Akiyoshi, Kozaburo;Ren, Xuefang;Ayala, Patricia;Burrows, Gregory G.;Vandenbark, Arthur A.;Herson, Paco S.;Hurn, Patricia D.;Offner, Halina A.
通讯作者：
Offner, Halina A.
影响因子：
4.4
作者：
Adamus, Grazyna;Brown, Lori;Vandenbark, Arthur A.
通讯作者：
Vandenbark, Arthur A.