Coimbra C, Drake M, Boris-Möller F, Wieloch T
Laboratory for Experimental Brain Research, Lund University, Sweden.
Stroke. 1996 Sep;27(9):1578-85. doi: 10.1161/01.str.27.9.1578.
It has been recognized that postischemic pharmacological interventions may delay the evolution of neuronal damage rather than provide long-lasting neuroprotection. Also, fever complicates recovery after stroke in humans. Here we report the effects of late postischemic treatment with hypothermia and an antipyretic/anti-inflammatory drug, dipyrone, on cell damage at 1 week and 2 months of survival.
Rats were subjected to 10 minutes of forebrain ischemia. Hypothermia (33 degrees C) was induced at 2 hours of recovery and maintained for 7 hours. Dipyrone (100 mg.kg-1IP) was given every 3 hours from 14 to 72 hours of recovery. Temperature was measured every 6 hours for 60 days. Neuronal damage was assessed at 7 days and 2 months of recovery.
From 17 to 72 hours of recovery, a period of hyperthermia was observed, which dipyrone abolished but postischemic hypothermia treatment did not. Dipyrone treatment diminished neuronal damage by 43% at 7 days, and at 2 months of survival, a minor (16%) protection was seen. Postischemic hypothermia treatment alone delayed neuronal damage. In contrast, combined treatment of hypothermia followed by dipyrone markedly diminished neuronal damage by more than 50% at both 7 days and 2 months of recovery.
Neuronal degeneration may be ongoing for months after a transient ischemic insult, and prolonged protective measures need to be instituted for long-lasting neuroprotective effects. Hyperthermia during recovery worsens ischemic damage, and processes associated with inflammation may contribute to the development of neuronal damage. An early and extended period of postischemic hypothermia provides a powerful and long-lasting protection if followed by treatment with anti-inflammatory/ antipyretic drug.
人们已经认识到，缺血后进行药物干预可能会延缓神经元损伤的进展，而非提供持久的神经保护作用。此外，发热会使人类中风后的恢复过程变得复杂。在此，我们报告缺血后晚期采用低温及一种解热/抗炎药物安乃近进行治疗，对存活1周和2个月时细胞损伤的影响。
对大鼠进行10分钟的前脑缺血。在恢复2小时时诱导低温（33摄氏度）并维持7小时。从恢复14至72小时期间，每3小时给予安乃近（100mg·kg-1腹腔注射）。在60天内每6小时测量一次体温。在恢复7天和2个月时评估神经元损伤情况。
在恢复17至72小时期间，观察到一段体温过高的时期，安乃近可消除该现象，但缺血后低温治疗则不能。安乃近治疗在7天时使神经元损伤减少了43%，在存活2个月时，可见轻微（16%）的保护作用。单独的缺血后低温治疗可延缓神经元损伤。相比之下，先进行低温治疗随后给予安乃近的联合治疗在恢复7天和2个月时均使神经元损伤显著减少超过50%。
短暂性缺血损伤后，神经元变性可能会持续数月，需要采取延长的保护措施以获得持久的神经保护作用。恢复期间体温过高会加重缺血损伤，与炎症相关的过程可能会促使神经元损伤的发展。如果在缺血后早期并延长低温治疗时间，随后给予抗炎/解热药物治疗，则可提供强大而持久的保护作用。
