Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent.
Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent.
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DOI：
10.1016/j.expneurol.2022.114136
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发表时间：
2022-09
影响因子：
5.3
通讯作者：
Baker, Kenneth B.
中科院分区：
文献类型：
--
作者：
Chan, Hugh H.;Hogue, Olivia;Mathews, Nicole D.;Hunter, Joshua G.;Kundalia, Ronak;Hermann, John K.;Floden, Darlene P.;Machado, Andre G.;Baker, Kenneth B.
关键词：
创伤性脑损伤(TBI)后的功能结果差异很大，尽管有现代的康复努力，但大约有一半的幸存者患有长期的运动和认知障碍。我们先前已经证明，小脑外侧核(LCN)的脑深部刺激(DBS)可以促进脑损伤引起的运动障碍的康复。本研究的目的是评价LCN DBS对啮齿类颅脑损伤患者康复的有效性，该模型独特地模拟了大多数人类颅脑损伤患者的损伤位置、慢性化和由此产生的认知症状。我们使用受控皮质撞击(CCI)造成以双侧内侧前额叶皮质(mPFC-CCI)为靶点的损伤，导致认知障碍。伤后6周行单侧LCN-DBS电极植入。电刺激在伤后第8周开始，并持续4周。采用诱饵Y迷宫、新物体识别任务和Barnes迷宫评价认知功能。死后分析，包括Western Blot和免疫组织化学，以阐明恢复的细胞和分子机制。我们发现，与损伤前和幼稚的动物相比，mPFC-CCI产生了显著的认知缺陷。此外，LCN DBS处理显著增强了应用策略的长时记忆加工和执行功能。死后组织分析显示，与未处理的动物相比，LCN DBS处理的动物在整个损毁皮质中CaMKIIα、BDNF和p75NTR的表达显著增加，突触后形成的表达也显著增加。总体而言，这些数据表明，LCN DBS是治疗脑外伤引起的认知障碍的有效方法，可能是通过激活向上的谷氨酸能投射到丘脑，随后上调丘脑皮质活动，从而参与促进功能重组的神经可塑性机制。这些结果支持小脑输出神经调节作为一种新的治疗方法来加强对对传统康复努力无效的慢性脑损伤后认知障碍患者的康复的作用。
Functional outcome following traumatic brain injury (TBI) varies greatly, with approximately half of those who survive suffering long-term motor and cognitive deficits despite contemporary rehabilitation efforts. We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) enhances rehabilitation of motor deficits that result from brain injury. The objective of the present study was to evaluate the efficacy of LCN DBS on recovery from rodent TBI that uniquely models the injury location, chronicity and resultant cognitive symptoms observed in most human TBI patients. We used controlled cortical impact (CCI) to produce an injury that targeted the medial prefrontal cortex (mPFC-CCI) bilaterally, resulting in cognitive deficits. Unilateral LCN DBS electrode implantation was performed six weeks post-injury. Electrical stimulation started at week eight post-injury and continued for an additional four weeks. Cognition was evaluated using baited Y-maze, novel object recognition task and Barnes maze. Post-mortem analyses, including Western Blot and immunohistochemistry, were conducted to elucidate the cellular and molecular mechanisms of recovery. We found that mPFC-CCI produced significant cognitive deficits compared to pre-injury and naïve animals. Moreover, LCN DBS treatment significantly enhanced the long-term memory process and executive functions of applying strategy. Analyses of post-mortem tissues showed significantly greater expression of CaMKIIα, BDNF and p75NTR across perilesional cortex and higher expression of postsynaptic formations in LCN DBS-treated animals compared to untreated. Overall, these data suggest that LCN DBS is an effective treatment of cognitive deficits that result from TBI, possibly by activation of ascending, glutamatergic projections to thalamus and subsequent upregulation of thalamocortical activity that engages neuroplastic mechanisms for facilitation of functional reorganization. These results support a role for cerebellar output neuromodulation as a novel therapeutic approach to enhance rehabilitation for patients with chronic, post-TBI cognitive deficits that are unresponsive to traditional rehabilitative efforts.
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影响因子：
5.3
作者：
Baker, Kenneth B.;Schuster, Daniel;Cooperrider, Jessica;Machado, Andre G.
通讯作者：
Machado, Andre G.
影响因子：
16.2
作者：
Dobbins, IG;Foley, H;Wagner, AD
通讯作者：
Wagner, AD
运动可改善血管性痴呆模型大鼠前额皮质的识别记忆和突触可塑性
影响因子：
1.9
作者：
Dong, Juntao;Zhao, Jingpu;Yan, Tiebin
通讯作者：
Yan, Tiebin
DOI：
10.1111/j.1365-2990.1985.tb00027.x
发表时间：
1985-01-01
影响因子：
5
作者：
ADAMS, JH;DOYLE, D;SAKAMOTO, T
通讯作者：
SAKAMOTO, T
DOI：
10.1111/j.1749-6632.2002.tb07575.x
发表时间：
2002-01-01
期刊：
CREBELLUM: RECENT DEVELOPMENTS IN CEREBELLAR RESEARCH
影响因子：
--
作者：
Dum, RP;Li, C;Strick, PL
通讯作者：
Strick, PL