The 'pharmacology' of neuronal rescue with cerebral hypothermia
The 'pharmacology' of neuronal rescue with cerebral hypothermia
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DOI：
10.1016/s0378-3782(98)00033-4
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发表时间：
1998-11-01
影响因子：
2.5
通讯作者：
Gunn, TR
中科院分区：
文献类型：
--
作者：
Gunn, AJ;Gunn, TR
低温在脑缺血或窒息时的神经保护作用是众所周知的。尽管，鉴于此，在从这种损伤复苏期间或之后低温的治疗作用的可能性一直是长期的研究焦点，但早期研究的结果有限且相互矛盾。临床上和实验上严重的围产期窒息性损伤与再灌注后的潜伏期有关，最初脑能量代谢恢复，但EEG抑制，随后是第二阶段，从出生后6至15小时癫痫发作，细胞毒性水肿，细胞毒素积累和脑能量衰竭。最近的研究提出了一个假设，即缺血后脑温度的变化可以严重调节脑病变过程，这些过程在缺氧缺血的初级阶段开始，但延伸到脑损伤的次级阶段。这个概念框架允许更好地理解决定有效低温神经保护的“药理学”参数，包括开始冷却的时间，它的持续时间和达到的冷却深度。中度脑低温起始于再灌注后1至6小时的潜伏期，并持续与脑损伤严重程度相关的足够持续时间，在成人和围产期物种中均与有效、持久的神经保护相关。这些令人鼓舞的结果必须与体温过低的不良全身效应相平衡。随机临床试验正在进行中，以确定长期脑低温的安全性和有效性。(C)1998爱思唯尔科学爱尔兰有限公司保留所有权利。
The neuroprotective effects of hypothermia during cerebral ischaemia or asphyxia are well known. Although, in view of this, the possibility of a therapeutic role for hypothermia during or after resuscitation from such insults has been a long standing focus of research, early studies had limited and contradictory results. Clinically and experimentally severe perinatal asphyxial injury is associated with a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase with seizures, cytotoxic edema, accumulation of cytotoxins, and cerebral energy failure from 6 to 15 h after birth. Recent studies have led to the hypothesis that changes in post-ischaemic cerebral temperature can critically modulate encephalopathic processes which are initiated during the primary phase of hypoxia-ischaemia, but which extend into the secondary phase of cerebral injury.This conceptual framework allows a better understanding of the 'pharmacological' parameters that determine effective hypothermic neuroprotection, including the timing of initiation of cooling, its duration and the depth of cooling attained. Moderate cerebral hypothermia initiated in the latent phase, between one and as late as 6 hours after reperfusion, and contined for a sufficient duration in relation to the severity of the cerebral injury, has been associated with potent, long-lasting neuroprotection in both adult and perinatal species. These encouraging results must be balanced against the adverse systemic effects of hypothermia. Randomised clinical trials are in progress to establish the safety and efficacy of prolonged cerebral hypothermia. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.