Klahr Ana C, Dietrich Kristen, Dickson Clayton T, Colbourne Frederick
1 Neuroscience and Mental Health Institute, University of Alberta , Edmonton, Canada .
2 Department of Psychology, University of Alberta , Edmonton, Canada .
Ther Hypothermia Temp Manag. 2016 Mar;6(1):40-7. doi: 10.1089/ther.2015.0028. Epub 2015 Dec 30.
Intracerebral hemorrhage (ICH) is a devastating stroke with high morbidity and mortality. Post-ICH seizures are a common complication, potentially increasing brain injury and the risk of delayed epilepsy. Mild therapeutic hypothermia (HYPO, ∼33°C) is neuroprotective against several brain insults, such as ischemia, while also mitigating seizure incidence and severity in some instances. Therefore, we tested whether brain-selective HYPO reduced electrographic seizure activity after a collagenase-induced striatal ICH in rats. Animals were injected unilaterally with 0.14 U of bacterial collagenase, implanted with a unilateral brain cooling device, and a probe to bilaterally record electroencephalographic (EEG) activity. Cooling began 6 hours after collagenase infusion and was maintained for 48 hours, followed by rewarming over 6 hours. Our protocol did not affect EEG activity in naïve rats, nor did it increase bleeding after ICH (∼50 μL). Epileptiform activity commonly occurred in untreated ICH rats (∼60% of animals), but HYPO did not affect the incidence, timing, total duration of seizures, or the peaks occurring during epileptiform activity. However, longer average duration was detected on the ipsilateral side to stroke in the HYPO group (p < 0.05). Cooling did not affect neurological deficits (e.g., circling), measured 7 and 14 days after ICH, or lesion volume (∼35 mm(3)). In addition, there was no relationship among endpoints (e.g., seizures and lesion size). In summary, HYPO failed to reduce seizure activity after ICH, which fits with our separate findings that cooling does not mitigate thrombin and iron-mediated secondary injury mechanisms thought to cause seizures after ICH. Additional research is needed to identify better HYPO protocols and the use of cotreatments to maximize the benefit of HYPO to ICH patients.
脑出血（ICH）是一种具有高发病率和死亡率的毁灭性中风。脑出血后癫痫发作是一种常见并发症，可能会加重脑损伤并增加迟发性癫痫的风险。轻度治疗性低温（HYPO，约33°C）对多种脑损伤具有神经保护作用，如缺血，同时在某些情况下还能降低癫痫发作的发生率和严重程度。因此，我们测试了脑选择性低温是否能降低大鼠胶原酶诱导的纹状体脑出血后的脑电图癫痫活动。动物单侧注射0.14 U细菌胶原酶，植入单侧脑冷却装置和双侧记录脑电图（EEG）活动的探头。冷却在胶原酶注入后6小时开始，持续48小时，随后在6小时内复温。我们的方案对未处理的大鼠脑电图活动没有影响，也没有增加脑出血后的出血量（约50 μL）。癫痫样活动在未治疗的脑出血大鼠中普遍发生（约60%的动物），但低温对癫痫发作的发生率、发作时间、发作总时长或癫痫样活动期间出现的峰值没有影响。然而，低温组中风同侧的平均发作时长更长（p < 0.05）。冷却不影响脑出血后7天和14天测量的神经功能缺损（如转圈）或损伤体积（约35 mm³）。此外，各终点指标之间没有关联（如癫痫发作和损伤大小）。总之，低温未能降低脑出血后的癫痫活动，这与我们另外的研究结果相符，即冷却不能减轻被认为是脑出血后癫痫发作原因的凝血酶和铁介导的继发性损伤机制。需要进一步研究以确定更好的低温方案以及联合治疗的使用，以最大化低温对脑出血患者的益处。
