Cell death after traumatic brain injury (TBI) is a major cause of neurological deficits and mortality. Understanding the mechanisms of delayed post-traumatic cell loss may lead to new therapies that improve outcome. Although TBI induces changes in multiple cell types, mechanisms of neuronal cell death have been the predominant focus. Recent work has emphasized the diversity of neuronal death phenotypes, which have generally been defined by either morphological or molecular changes. This diversity has led to confusing and at times contradictory nomenclature. Here we review the historical basis of proposed definitions of neuronal cell death, with the goal of clarifying critical research questions and implications for therapy in TBI. We believe that both morphological and molecular features must be used to clarify post-traumatic cell death and related therapeutic targets. Further, we underscore that the most effective neuroprotective strategies will need to target multiple pathways to reflect the regional and temporal changes underlying diverse neuronal cell death phenotypes.

中文翻译：

---

创伤性脑损伤中的细胞死亡机制和调节。

外伤性脑损伤 (TBI) 后的细胞死亡是神经功能缺损和死亡的主要原因。了解延迟的创伤后细胞丢失的机制可能会导致改善结果的新疗法。尽管 TBI 会引起多种细胞类型的变化，但神经元细胞死亡的机制一直是主要焦点。最近的工作强调了神经元死亡表型的多样性，这些表型通常由形态或分子变化来定义。这种多样性导致了令人困惑且有时相互矛盾的命名法。在这里，我们回顾了提出的神经元细胞死亡定义的历史基础，目的是澄清关键的研究问题和对 TBI 治疗的影响。我们认为必须同时使用形态学和分子特征来阐明创伤后细胞死亡和相关的治疗靶点。此外，我们强调，最有效的神经保护策略需要针对多种途径，以反映不同神经元细胞死亡表型背后的区域和时间变化。