创伤性脑水肿的形成机制和治疗

Formation Mechanism and Treatment of Traumatic Brain Edema

摘要: 研究创伤性脑损伤(TBI, Traumatic brain injury)的复杂分子机制对于开发新的TBI疗法至关重要。目前对TBI的治疗主要集中在稳定患者生命体征和缓解症状上。然而，该领域缺乏预防细胞死亡、氧化应激和炎症等的方法，这些都会导致慢性病理。创伤的早期特征包括脑实质损伤、脑出血、轴索伤等。继发性损伤从原发性损伤后的几小时、几天或几个月陆续出现，包括炎症、脑水肿、血脑屏障(BBB, Blood-brain barrier)破裂、氧化应激、兴奋性毒性以及线粒体和代谢功能障碍等，继发性损伤极大地影响了患者临床预后。从长期的临床工作来看，在TBI的诸多并发症中，尤以脑水肿(CE, Cerebral edema)最多见，急性期常给患者带来痛苦和脑疝的风险。目前CE的治疗多为非特异性的，如去骨瓣减压、低温疗法、渗透疗法等，但对于中、重型TBI患者，水肿一旦形成，临床治疗效果往往不令人满意。因此，从消除水肿到预防水肿的形成这种治疗上的转变是很有必要的。本文结合目前创伤性脑水肿的研究进展对TBI后CE形成的病理生理机制、靶向药物和后期神经功能康复进行了一次综述。

Abstract: The study of the complex molecular mechanisms of traumatic brain injury (TBI) is critical to the development of new TBI therapies. Current treatments for TBI focus on stabilizing patients’ vital signs and alleviating symptoms. However, the field lacks methods to prevent cell death, oxidative stress and inflammation, which all contribute to chronic pathology. Early features of trauma include brain parenchymal injury, cerebral hemorrhage, axonal injury, etc. Secondary injuries, including inflammation, cerebral edema, rupture of the blood-brain barrier (BBB), oxidative stress, excitatory toxicity, and mitochondrial and metabolic dysfunction, appear in the hours, days, or months after the primary injury, and greatly affect the clinical outcome of the patients. From the perspective of long-term clinical work, cerebral edema (CE) is the most common complication of TBI, and the acute phase often brings pain and the risk of cerebral hernia to patients. At present, the treatment of CE is mostly non-specific, such as decompression of bone flap, hypothermia therapy, osmotic therapy, etc. However, for patients with moderate or severe TBI, once edema forms, the clinical treatment effect is often unsatisfactory. Therefore, it is necessary to make a change in treatment from eliminating edema to preventing its formation. In this review, we reviewed the pathophysiological mechanism of CE formation after TBI, targeted drugs and rehabilitation of neurological function in combination with the current research progress of traumatic brain edema.