McIntosh T K
Department of Surgery, University of Pennsylvania, Philadelphia 19104.
Cerebrovasc Brain Metab Rev. 1994 Summer;6(2):109-62.
The cerebrovascular and metabolic changes associated with traumatic injury to the CNS may be associated, in part, with pathologic alterations in endogenous neurochemical systems, including those involved with normal neurotransmission. These events may include alterations in neurotransmitter synthesis, release, or re-uptake mechanisms or changes in pre- or postsynaptic receptor activity. Other changes may include alterations in synthesis and release of endogenous neuroprotective compounds (e.g., antioxidants), the pathologic expression and release of endogenous "autodestructive" compounds, or regional changes in specific neurochemical factors known to be associated with inflammation (e.g., cytokines), or neuronal growth and regeneration (e.g., growth factors). Although the timing of the precise cascade of neurochemical events following CNS injury is poorly understood, recent identification of specific neurochemical alterations following traumatic brain injury provides an opportunity for the development and employment of therapeutic agents designed to modify gene expression, synthesis, release, receptor, or functional activity of these factors with subsequent attenuation of local secondary tissue damage. This article is a compendium of recent studies suggesting that modification of posttraumatic events with pharmacologic strategies can improve outcome and promote functional recovery in both animal models of traumatic CNS injury and in selected clinical trials.
与中枢神经系统创伤性损伤相关的脑血管和代谢变化，可能部分与内源性神经化学系统的病理改变有关，包括那些参与正常神经传递的系统。这些事件可能包括神经递质合成、释放或再摄取机制的改变，或突触前或突触后受体活性的变化。其他变化可能包括内源性神经保护化合物（如抗氧化剂）合成和释放的改变、内源性“自毁性”化合物的病理表达和释放，或已知与炎症（如细胞因子）或神经元生长和再生（如生长因子）相关的特定神经化学因子的区域变化。尽管对中枢神经系统损伤后精确的神经化学事件级联发生的时间了解甚少，但最近对创伤性脑损伤后特定神经化学改变的识别，为开发和应用旨在改变这些因子的基因表达、合成、释放、受体或功能活性，从而随后减轻局部继发性组织损伤的治疗药物提供了机会。本文是近期研究的综述，表明在创伤性中枢神经系统损伤的动物模型和选定的临床试验中，采用药理学策略改变创伤后事件可改善预后并促进功能恢复。
