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首页> 外文期刊>Brain research >Levetiracetam increases neonatal hypoxic-ischemic brain injury under normothermic, but not hypothermic conditions
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Levetiracetam increases neonatal hypoxic-ischemic brain injury under normothermic, but not hypothermic conditions

机译：左乙拉西坦在常温下而非低温条件下增加新生儿缺氧缺血性脑损伤

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Background: Hypoxic-ischemic encephalopathy (HIE) resulting from perinatal asphyxia often leads to severe neurologic impairment or even death. There is a need to advance therapy for infants with HIE, for example to combine hypothermia with pharmacological treatment strategies. Levetiracetam (LEV) is approved for clinical administration to infants older than 4 weeks of age and is also used off-label in neonates. Furthermore, LEV was shown to be neuroprotective in adult animal models of brain injury.Aim of the study: The aim of this study was to evaluate the neuroprotective potential of LEV in vitro using primary hippocampal neurons, and in vivo using an established model of neonatal hypoxic-ischemic brain injury.Results: LEV treatment per se did not induce neurotoxicity in the developing rodent brain. Following oxygen glucose deprivation, we observed some, although not a significant, increase in cell death after LEV treatment. In vivo, LEV was administered under normothermic and hypothermic conditions following hypoxic-ischemic brain damage. LEV administration significantly increased brain injury under normothermic conditions. Compared to the normothermia-treated group, in the hypothermia group LEV administration did not increase hypoxic-ischemic brain injury.Discussion: This study demonstrates that LEV treatment increases neonatal hypoxic-ischemic brain injury. Administration of LEV in the acute phase of the injury might interfere with the balanced activation and inactivation of excitatory and inhibitory receptors in the developing brain. The neurotoxic effect of LEV in the injured newborn brain might further suggest an agonistic effect of LEV on the GABAergic system. Hypothermia treatment attenuates glutamate release following hypoxic-ischemic brain injury and might therefore limit the potentially deleterious effects of LEV. As a consequence, our findings do not necessarily rule out a potentially beneficial effect, but argue for cautious use of LEV in newborn infants with pre-existing brain injury.
机译：背景：围产期窒息引起的缺氧缺血性脑病（HIE）通常会导致严重的神经系统损害甚至死亡。需要对患有HIE的婴儿进行先进的治疗，例如将体温过低与药物治疗策略相结合。左乙拉西坦（LEV）已获批准可对4周龄以上的婴儿进行临床给药，并且在新生儿中也可在标签外使用。此外，LEV被证明在成年动物脑损伤模型中具有神经保护作用。研究目的：本研究的目的是评估在体外使用原代海马神经元对LEV的神经保护潜力，并在体内使用已建立的新生儿模型对LEV进行神经保护。结果：LEV治疗本身并未在发育中的啮齿动物大脑中引起神经毒性。氧葡萄糖剥夺后，我们观察到LEV治疗后细胞死亡有所增加，尽管不是很明显。在体内，在缺氧缺血性脑损伤后，在常温和低温条件下施用LEV。在常温条件下，LEV给药显着增加了脑损伤。与正常体温治疗组相比，在低温治疗组中LEV给药不会增加缺氧缺血性脑损伤。讨论：这项研究表明，LEV治疗会增加新生儿缺氧缺血性脑损伤。在损伤的急性期给予LEV可能会干扰发育中的大脑中兴奋性和抑制性受体的平衡激活和失活。 LEV在受伤的新生脑中的神经毒性作用可能进一步提示LEV对GABA能系统的激动作用。低温治疗可减轻缺氧缺血性脑损伤后谷氨酸的释放，因此可能会限制LEV的潜在有害作用。结果，我们的发现并不一定排除潜在的有益作用，而是主张对患有先天性脑损伤的新生儿谨慎使用LEV。

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