Genetic Deletion of PGF(2α)-FP Receptor Exacerbates Brain Injury Following Experimental Intracerebral Hemorrhage.
Genetic Deletion of PGF(2α)-FP Receptor Exacerbates Brain Injury Following Experimental Intracerebral Hemorrhage.
复制标题
DOI：
10.3389/fnins.2018.00556
复制
发表时间：
2018
影响因子：
4.3
通讯作者：
Doré S
中科院分区：
文献类型：
--
作者：
Mohan S;Koller EJ;Fazal JA;De Oliveria G;Pawlowicz AI;Doré S
背景：炎性分子的释放，如胰高血糖素（例如，PGF 2 α）与脑出血性（ICH）卒中后的脑损伤相关;然而，PGF 2 α及其同源FP受体在ICH中的作用仍不清楚。本研究的重点是在ICH临床前模型中研究FP受体作为新型神经保护药物靶点的作用，旨在研究PGF 2 α-FP轴在调节ICH后功能恢复和解剖结局中的作用。结果：FP−/−小鼠在ICH后72 h的神经功能缺损评分显著高于WT小鼠（6.1 ± 0.7 vs. 3.1 ± 0.8; P < 0.05）。评估运动技能，与WT小鼠相比，FP−/−小鼠在ICH后24小时停留在旋转杆上的总时间显著更短（27.0 ± 7.5 vs. 52.4 ± 11.2 s; P < 0.05）。使用握力量化前爪力量，结果显示，FP−/−小鼠在ICH后72小时的力量显著低于WT小鼠（96.4 ± 17.0 vs. 129.6 ± 5.9 g; P < 0.01）。除了行为结果外，还进行了组织病理学测量。在甲酚紫染色的脑切片中，FP−/−小鼠的病变体积显著大于WT小鼠（15.0 ± 2.2 vs. 3.2 ± 1.7 mm 3; P < 0.05小鼠）。为了估计血肿周围区域中三价铁的存在，进行了Perls染色，结果显示FP−/−小鼠的染色显著高于WT小鼠（186.3 ± 34.4% vs. 86.9 ± 13.0%总阳性像素计数，P < 0.05）。对FP−/−和WT小鼠ICH后的脑切片进行免疫反应性实验，以分别使用针对Iba 1和GFAP的抗体监测小胶质细胞增生和星形胶质细胞增生的变化。这些实验表明，FP−/−小鼠在ICH后比WT小鼠具有更大的星形胶质细胞增生趋势。结论：我们发现，与WT匹配的对照组相比，PGF 2 α FP受体的缺失加重了ICH后的行为障碍并增加了病灶体积。
Background: The release of inflammatory molecules such as prostaglandins (e.g., PGF2α) is associated with brain damage following an intracerebral hemorrhagic (ICH) stroke; however, the role of PGF2α and its cognate FP receptor in ICH remains unclear. This study focused on investigating the role of the FP receptor as a target for novel neuroprotective drugs in a preclinical model of ICH, aiming to investigate the contribution of the PGF2α-FP axis in modulating functional recovery and anatomical outcomes following ICH. Results: Neurological deficit scores in FP−/− mice were significantly higher compared to WT mice 72 h after ICH (6.1 ± 0.7 vs. 3.1 ± 0.8; P < 0.05). Assessing motor skills, the total time mice stayed on the rotating rod was significantly less in FP−/−mice compared to WT mice 24 h after ICH (27.0 ± 7.5 vs. 52.4 ± 11.2 s; P < 0.05). Using grip strength to quantify forepaw strength, results showed that the FP−/− mice had significantly less strength compared to WT mice 72 h after ICH (96.4 ± 17.0 vs. 129.6 ± 5.9 g; P < 0.01). In addition to the behavioral outcomes, histopathological measurements were made. In Cresyl violet stained brain sections, the FP−/− mice showed a significantly larger lesion volume compared to the WT (15.0 ± 2.2 vs. 3.2 ± 1.7 mm3; P < 0.05 mice.) To estimate the presence of ferric iron in the peri-hematoma area, Perls' staining was performed, which revealed that FP−/− mice had significantly greater staining than the WT mice (186.3 ± 34.4% vs. 86.9 ± 13.0% total positive pixel counts, P < 0.05). Immunoreactivity experiments on brain sections from FP−/− and WT mice post-ICH were performed to monitor changes in microgliosis and astrogliosis using antibodies against Iba1 and GFAP respectively. These experiments showed that FP−/− mice had a trend toward greater astrogliosis than WT mice post-ICH. Conclusion: We showed that deletion of the PGF2α FP receptor exacerbates behavioral impairments and increases lesion volumes following ICH compared to WT-matched controls.Detailed mechanisms responsible for these novel results are actively being pursued.
登录
查看更多内容
影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
前列腺素E2 EP2受体缺失减弱脑出血引起的脑损伤并改善功能恢复。
影响因子：
4.7
作者：
Leclerc JL;Lampert AS;Diller MA;Immergluck JB;Doré S
通讯作者：
Doré S
影响因子：
2.9
作者：
Gibbons, Hannah M.;Dragunow, Mike
通讯作者：
Dragunow, Mike
影响因子：
4.2
作者：
Saleem, Sofiyan;Li, Rung-Chi;Dore, Sylvain
通讯作者：
Dore, Sylvain
影响因子：
8.3
作者：
Choudhri, TF;Hoh, BL;Pinsky, DJ
通讯作者：
Pinsky, DJ