Modeling Traumatic Brain Injury in Human Cerebral Organoids.
Modeling Traumatic Brain Injury in Human Cerebral Organoids.
复制标题
在人脑类器官中模拟创伤性脑损伤。
作者：
Ramirez S;Mukherjee A;Sepulveda S;Becerra-Calixto A;Bravo-Vasquez N;Gherardelli C;Chavez M;Soto C
创伤性脑损伤（TBI）是一种破坏正常大脑结构和功能的头部损伤。 TBI 已使用各种体外和体内模型进行了广泛研究。大多数研究都是在啮齿动物模型上进行的，这些模型对 TBI 的反应可能与人类神经细胞不同。利用最近开发的源自人类诱导多能干细胞 (iPSC) 的脑类器官 (CO)（类似于人类特定大脑区域的结构），我们采用受控皮质冲击 (CCI) 模型作为新型体外平台在人类 CO 中诱导 TBI。为了使 CCI 程序适应 CO，我们开发了一个幻脑矩阵，与大脑的机械特性相匹配，并以空的小鼠头骨作为平台，允许在 CO 上使用立体定向 CCI 设备。 CCI 程序后，使用微管相关蛋白 2 (MAP2) 和胶质纤维酸性蛋白 (GFAP) 对 CO 进行组织学制备，以评估神经元和星形胶质细胞群。此外，还分析了代谢反应的标志物、神经元特异性烯醇化酶 (NSE) 和使用裂解的 caspase 3 的细胞死亡。我们的结果表明，人类 CO 概括了 TBI 的主要病理变化，包括与神经元损伤、神经元丢失和星形胶质细胞增生相关的代谢改变。这种使用人类CO在体外模拟TBI的新方法具有巨大的潜力，为理解TBI产生的大脑异常以及开发和测试新的治疗方法开辟了新的替代方案。
Traumatic brain injury (TBI) is a head injury that disrupts the normal brain structure and function. TBI has been extensively studied using various in vitro and in vivo models. Most of the studies have been done with rodent models, which may respond differently to TBI than human nerve cells. Taking advantage of the recent development of cerebral organoids (COs) derived from human induced pluripotent stem cells (iPSCs), which resemble the architecture of specific human brain regions, here, we adapted the controlled cortical impact (CCI) model to induce TBI in human COs as a novel in vitro platform. To adapt the CCI procedure into COs, we have developed a phantom brain matrix, matching the mechanical characteristics of the brain, altogether with an empty mouse skull as a platform to allow the use of the stereotactic CCI equipment on COs. After the CCI procedure, COs were histologically prepared to evaluate neurons and astrocyte populations using the microtubule-associated protein 2 (MAP2) and the glial fibrillary acidic protein (GFAP). Moreover, a marker of metabolic response, the neuron-specific enolase (NSE), and cellular death using cleaved caspase 3 were also analyzed. Our results show that human COs recapitulate the primary pathological changes of TBI, including metabolic alterations related to neuronal damage, neuronal loss, and astrogliosis. This novel approach using human COs to model TBI in vitro holds great potential and opens new alternatives for understanding brain abnormalities produced by TBI, and for the development and testing of new therapeutic approaches.
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影响因子：
11
作者：
Gonzalez C;Armijo E;Bravo-Alegria J;Becerra-Calixto A;Mays CE;Soto C
通讯作者：
Soto C
DOI：
10.3389/fnene.2013.00008
发表时间：
2013-10-04
期刊：
Frontiers in neuroenergetics
影响因子：
--
作者：
Bartnik-Olson BL;Harris NG;Shijo K;Sutton RL
通讯作者：
Sutton RL
影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
影响因子：
5.3
作者：
Burda JE;Bernstein AM;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
16.2
作者：
Abud EM;Ramirez RN;Martinez ES;Healy LM;Nguyen CHH;Newman SA;Yeromin AV;Scarfone VM;Marsh SE;Fimbres C;Caraway CA;Fote GM;Madany AM;Agrawal A;Kayed R;Gylys KH;Cahalan MD;Cummings BJ;Antel JP;Mortazavi A;Carson MJ;Poon WW;Blurton-Jones M
通讯作者：
Blurton-Jones M