A GSK-3β inhibitor protects against radiation necrosis in mouse brain.
A GSK-3β inhibitor protects against radiation necrosis in mouse brain.
复制标题
DOI：
10.1016/j.ijrobp.2014.04.018
复制
发表时间：
2014-07-15
影响因子：
7
通讯作者：
Garbow, Joel R.
中科院分区：
文献类型：
--
作者：
Jiang, Xiaoyu;Perez-Torres, Carlos J.;Thotala, Dinesh;Engelbach, John A.;Yuan, Liya;Cates, Jeremy;Gao, Feng;Drzymala, Robert E.;Rich, Keith M.;Schmidt, Robert E.;Ackerman, Joseph J. H.;Hallahan, Dennis E.;Garbow, Joel R.
To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant of radiation-induced, CNS (brain) necrosis in a mouse model. Cohorts of mice were treated with SB415286 or DMSO prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by non-invasive in vivo, small-animal MRI, beginning 13 weeks post-irradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all post-irradiation time points in SB415286-treated animals. While the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemisphere of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. The unilateral cerebral hemispheric stereotactic radiosurgery mouse model, in concert with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new neuroprotectants. SB415286’s effectiveness as a neuroprotectant for necrosis motivates potential clinical trials of it or other GSK-3β inhibitors.
登录
查看更多内容
DOI：
10.1016/j.ijrobp.2009.09.024
发表时间：
2010-02-01
影响因子：
7
作者：
Thotala, Dinesh K.;Geng, Ling;Dickey, Amy K.;Hallahan, Dennis E.;Yazlovitskaya, Eugenia M.
通讯作者：
Yazlovitskaya, Eugenia M.
DOI：
10.1016/j.ijrobp.2009.12.061
发表时间：
2011-04-01
影响因子：
7
作者：
Levin, Victor A.;Bidaut, Luc;Hou, Ping;Kumar, Ashok J.;Wefel, Jeffrey S.;Bekele, B. Nebiyou;Prabhu, Sujit;Loghin, Monica;Gilbert, Mark R.;Jackson, Edward F.
通讯作者：
Jackson, Edward F.
DOI：
10.1016/j.ijrobp.2005.12.002
发表时间：
2006-06-01
影响因子：
7
作者：
Ruben, Jeremy D.;Dally, Michael;Fedele, Pasqual
通讯作者：
Fedele, Pasqual
影响因子：
5.7
作者：
Flickinger, JC;Kondziolka, D;Lunsford, LD
通讯作者：
Lunsford, LD
影响因子：
11.2
作者：
Thotala, Dinesh K.;Hallahan, Dennis E.;Yazlovitskaya, Eugenia M.
通讯作者：
Yazlovitskaya, Eugenia M.