Hakon Jakob, Ruscher Karsten, Romner Bertil, Tomasevic Gregor
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, Lund, Sweden; Department of Neurosurgery, Copenhagen University Hospital, Risgshospitalet, Denmark.
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, Lund, Sweden.
PLoS One. 2015 Mar 30;10(3):e0120074. doi: 10.1371/journal.pone.0120074. eCollection 2015.
Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.
脑水肿是中重度创伤性脑损伤（TBI）后的常见并发症，也是神经元死亡和神经功能恶化的重要危险因素。迄今为止，尚无有效减轻TBI后脑水肿和神经元死亡的医学方法。胰高血糖素样肽-1（GLP-1）对脑内皮具有抗炎特性，并发挥神经保护作用。在此，我们研究了GLP-1对中重度TBI后继发性损伤的影响。将雄性Sprague Dawley大鼠通过控制性皮质撞击（CCI）造成TBI或进行假手术。术后，每天两次皮下注射载体或GLP-1类似物利拉鲁肽，持续两天。利拉鲁肽（200μg/kg）治疗显著减轻了CCI后48小时挫伤周围区域的脑水肿，并改善了感觉运动功能。通过伊文思蓝结合白蛋白的脑外渗测定，利拉鲁肽治疗的动物血脑屏障的完整性得到显著保留。此外，利拉鲁肽减少了皮质组织损失，但在损伤后第7天对丘脑的组织损失和延迟性神经元死亡没有影响。总之，我们的数据表明，GLP-1途径可能是中重度TBI后脑水肿和皮质神经元损伤治疗的一个有前景的靶点。
