Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats.
Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats.
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DOI：
10.3389/fneur.2018.00451
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发表时间：
2018
影响因子：
3.4
通讯作者：
Jantzie LL
中科院分区：
文献类型：
--
作者：
Robinson S;Winer JL;Chan LAS;Oppong AY;Yellowhair TR;Maxwell JR;Andrews N;Yang Y;Sillerud LO;Meehan WP 3rd;Mannix R;Brigman JL;Jantzie LL
婴儿创伤性脑损伤（TBI）的幸存者容易出现慢性神经功能缺损，这给个人和社会带来了终身的负担。将新的干预措施转化为临床试验在一定程度上受到缺乏真正代表性的认知临床前试验和相应的功能结果生物标志物的阻碍。为了解决这一差距，在大鼠出生后12天（P12）控制皮质撞击（CCI）模型中，使用触摸屏操作室和弥散张量成像（DTI）的区域分析，测试了高剂量、延长的促红细胞生成素（EPO，3000 U/kg/剂量× 6 d）损伤后治疗方案预防慢性认知和成像缺陷的能力。结果表明，EPO预防婴儿TBI后的功能损伤和MRI损伤。具体而言，亚急性DTI在P30揭示了广泛的微结构损伤，防止EPO。在触摸屏操作室平台上进行的视觉辨别评估表明，所有组都可以进行视觉辨别。然而，与假手术和CCI-EPO大鼠相比，用载体处理的CCI大鼠未能通过逆转学习，并且持续。P90的慢性DTI显示EPO治疗预防了对侧白色物质和同侧外侧前额叶皮质的损伤。这种DTI改善与认知表现相关。总之，在婴儿TBI的转化临床前模型中，延长的EPO治疗恢复了具有认知缺陷的成年大鼠的执行功能并防止了微结构脑异常。使用触摸屏操作室和区域DTI分析的复杂测试可以加快从临床前研究到临床试验的干预措施的转化和有效产量。总的来说，这些数据支持EPO在TBI婴儿临床试验中的应用。
Survivors of infant traumatic brain injury (TBI) are prone to chronic neurological deficits that impose lifelong individual and societal burdens. Translation of novel interventions to clinical trials is hampered in part by the lack of truly representative preclinical tests of cognition and corresponding biomarkers of functional outcomes. To address this gap, the ability of a high-dose, extended, post-injury regimen of erythropoietin (EPO, 3000U/kg/dose × 6d) to prevent chronic cognitive and imaging deficits was tested in a postnatal day 12 (P12) controlled-cortical impact (CCI) model in rats, using touchscreen operant chambers and regional analysis of diffusion tensor imaging (DTI). Results indicate that EPO prevents functional injury and MRI injury after infant TBI. Specifically, subacute DTI at P30 revealed widespread microstructural damage that is prevented by EPO. Assessment of visual discrimination on a touchscreen operant chamber platform demonstrated that all groups can perform visual discrimination. However, CCI rats treated with vehicle failed to pass reversal learning, and perseverated, in contrast to sham and CCI-EPO rats. Chronic DTI at P90 showed EPO treatment prevented contralateral white matter and ipsilateral lateral prefrontal cortex damage. This DTI improvement correlated with cognitive performance. Taken together, extended EPO treatment restores executive function and prevents microstructural brain abnormalities in adult rats with cognitive deficits in a translational preclinical model of infant TBI. Sophisticated testing with touchscreen operant chambers and regional DTI analyses may expedite translation and effective yield of interventions from preclinical studies to clinical trials. Collectively, these data support the use of EPO in clinical trials for human infants with TBI.
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影响因子：
4.2
作者：
Dennis, Emily L.;Jin, Yan;Villalon-Reina, Julio E.;Zhan, Liang;Kernan, Claudia L.;Babikian, Talin;Mink, Richard B.;Babbitt, Christopher J.;Johnson, Jeffrey L.;Giza, Christopher C.;Thompson, Paul M.;Asarnow, Robert F.
通讯作者：
Asarnow, Robert F.
影响因子：
2.9
作者：
Jantzie LL;Winer JL;Corbett CJ;Robinson S
通讯作者：
Robinson S
精神分裂症认知临床前模型的新转化测定：小鼠和大鼠的触摸屏测试方法。
影响因子：
4.7
作者：
Bussey TJ;Holmes A;Lyon L;Mar AC;McAllister KA;Nithianantharajah J;Oomen CA;Saksida LM
通讯作者：
Saksida LM
DOI：
10.3390/ijerph14040414
发表时间：
2017-04-13
影响因子：
--
作者：
Chen C;Shi J;Stanley RM;Sribnick EA;Groner JI;Xiang H
通讯作者：
Xiang H
影响因子：
25
作者：
Graybeal C;Feyder M;Schulman E;Saksida LM;Bussey TJ;Brigman JL;Holmes A
通讯作者：
Holmes A