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Perspectives for computational modeling of cell replacement for neurological disorders

机译:用于神经系统疾病的细胞置换计算模型的观点

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摘要

Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.
机译:解剖学上受约束的神经网络的数学模型为网络对神经系统疾病或损伤的反应提供了重要的见识。这些模型的逻辑扩展是合并治疗方案以调查网络对干预的反应。近几十年来,已将来自干细胞前体的新生神经元添加到受损或患病的组织中已用作成功的治疗工具。有趣的是,已经开发了模型来检查新的神经元是否整合到完整的成人结构中,特别是海马的齿状颗粒神经元。这些研究表明,成熟的神经元的独特特性会以意想不到的方式影响电路行为。从这个角度出发,我们回顾了用于检查受损中枢神经系统结构的模型的当前状态,尤其关注中风引起的皮质损伤。其次,我们建议通过实施当前成人神经发生模型所采用的方法,可以使细胞替代疗法的计算模型可行。这些模型的开发对于生成有关移植疗法的假设以及通过使移植适应所需的效果改善结果至关重要。

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