COG1410 improves cognitive performance and reduces cortical neuronal loss in the traumatically injured brain.
COG1410 improves cognitive performance and reduces cortical neuronal loss in the traumatically injured brain.
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DOI：
10.1089/neu.2008.0565
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发表时间：
2009-01
影响因子：
4.2
通讯作者：
McKenna SE
中科院分区：
文献类型：
--
作者：
Hoane MR;Kaufman N;Vitek MP;McKenna SE
我们以前已经证明，单剂量的COG 1410，一种小分子ApoE模拟肽衍生自载脂蛋白E（ApoE）受体结合区，改善感觉运动和运动的结果后，皮质挫伤损伤（CCI）。本研究评估了额叶CCI后的COG 1410方案，以检查其对认知恢复的临床前疗效。用额叶皮质的双侧CCI制备动物。在CCI后30分钟和24小时再次给予两次COG 1410方案（0.8 mg/kg静脉内[IV]）。从第11天开始，测试动物在Morris水迷宫（MWM）中获得参考记忆任务，然后在第15天在MWM中获得工作记忆任务。CCI后，还对动物进行双侧触觉粘合剂去除试验，以测量感觉运动功能障碍。在所有的行为测试中，COG 1410组与未受伤的假手术组没有区别。施用方案的COG 1410显著改善了参考和工作记忆测试以及感觉运动测试的恢复。损伤分析显示，COG 1410显著减小了损伤腔的大小。在CCI后48小时，通过Fluoro-Jade C染色测量，给予COG 1410还减少了额叶皮质中变性神经元的数量。这些结果表明，COG 1410的方案似乎阻断了显著行为缺陷的发展并减少了组织损失。这些组合的发现表明，当在创伤性脑损伤（TBI）后施用时，COG 1410似乎具有强的临床前功效。
We have previously shown that a single dose of COG1410, a small molecule ApoE-mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region, improves sensorimotor and motor outcome following cortical contusion injury (CCI). The present study evaluated a regimen of COG1410 following frontal CCI in order to examine its preclinical efficacy on cognitive recovery. Animals were prepared with a bilateral CCI of the frontal cortex. A regimen of COG1410 (0.8 mg/kg intravenously [IV]) was administered twice, at 30 min and again at 24 h post-CCI. Starting on day 11, the animals were tested for their acquisition of a reference memory task in the Morris water maze (MWM), followed by a working memory task in the MWM on day 15. Following CCI, the animals were also tested on the bilateral tactile adhesive removal test to measure sensorimotor dysfunction. On all of the behavioral tests the COG1410 group was no different from the uninjured sham group. Administration of the regimen of COG1410 significantly improved recovery on the reference and working memory tests, as well as on the sensorimotor test. Lesion analysis revealed that COG1410 significantly reduced the size of the injury cavity. Administration of COG1410 also reduced the number of degenerating neurons, as measured by Fluoro-Jade C staining, in the frontal cortex at 48 h post-CCI. These results suggest that a regimen of COG1410 appeared to block the development of significant behavioral deficits and reduced tissue loss. These combined findings suggest that COG1410 appears to have strong preclinical efficacy when administered following traumatic brain injury (TBI).
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影响因子：
3.5
作者：
Laskowitz, D. T.;Fillit, H.;Vitek, M. P.
通讯作者：
Vitek, M. P.
影响因子：
5.3
作者：
Laskowitz, DT;Thekdi, AD;Bennett, ER
通讯作者：
Bennett, ER
影响因子：
5.1
作者：
Fitch, R. Holly;Breslawski, Heather;Chrobak, James J.
通讯作者：
Chrobak, James J.
DOI：
10.1016/s0925-4439(99)00010-1
发表时间：
1999-03-30
影响因子：
6.2
作者：
Lomnitski, L;Chapman, S;Michaelson, DM
通讯作者：
Michaelson, DM
影响因子：
2.5
作者：
McAdoo, JD;Warner, DS;Laskowitz, DT
通讯作者：
Laskowitz, DT