中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1379-1380.

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

常规脑外科手术中黄体酮会是比地塞米松更好的选择吗?

  

  • 收稿日期:2015-06-16 出版日期:2015-09-28 发布日期:2015-09-28

Can progesterone be a better alternative to dexamethasone for use in routine brain surgery?

Stephen Y. Cheng, Gilberto K. K. Leung   

  1. Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China
  • Received:2015-06-16 Online:2015-09-28 Published:2015-09-28
  • Contact: Gilberto K. K. Leung, Ph.D., gilberto@hku.hk.

摘要:

外科性脑损伤是由神经外科干预造成,如脑肿瘤切除术、癫痫外科治疗的脑叶切除术士造成的脑创伤。脑水肿和脑肿胀通常在外科脑损伤后不久即会发生,峰值通常出现在术后3-7天。由于血脑屏障破裂,炎性细胞因子(如肿瘤坏死因子,白细胞介素-1, 6,toll样受体-2,4,)的释放,以及Fas及其Fas-L的增加表达,自由基过载,细胞膜离子原功能障碍等诸多病理生理改变,导致二次损害的发生。严重的脑水肿最终可导致颅内压增高,神经功能恶化甚至死亡。而对其他幸存者造成的长期影响包括继发性和延迟性退行性变造成的感觉运动以及认知功能障碍。鉴于每一天在全球范围内都会进行大量常规神经外科手术,预防外科脑损伤与事故造成的创伤性脑损伤治疗同样重要。在这些情况下如何最有效地预防脑水肿和继发性损伤,这个问题非常关键,是值得开展研究工作的。传统上来说,地塞米松和其他糖皮质激素广泛已用来作为辅助剂在神经外科手术中减轻脑水肿,维持血脑屏障完整性并减少炎症反应。这种方法自20世纪60年代以来开始在创伤性脑损伤患者中使用,然而,1979年至2004年间进行的多次重大的研究表明,在严重创伤性脑损伤手术中使用糖皮质激素并没有任何好处,甚至可能是有害的。因此,在这方面,Gilberto K. K. Leung和他的研究小组成员的一直在研究外科脑损伤治疗的替代策略。

Abstract:

Surgical brain injury (SBI) is a form of brain trauma caused by various forms of neurosurgical interventions including brain tumor excision, evacuation of intracerebral hemorrhage and brain lobectomy (e.g., in epilepsy surgery). Cerebral edema and brain swelling typically occurs soon after SBI and commonly peaks on post-operative day 3 to 7. SBI may cause secondary damages due to disruption of the blood–brain barrier (BBB), release of inflammatory cytokines (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, toll-like receptor (TLR-2) and TLR-4,) as well as increased expressions of Fas and Fas-L, free radical overload, dysfunctions of membrane ionic pumps and many other pathophysiological changes. Severe cerebral edema may eventually lead to elevated intracranial pressure (ICP), neurological deterioration or even death. Other long-term effects in survivors include sensori-motor and cognitive dysfunctions due to secondary, delayed degenerative changes. Given the large number of routine neurosurgical operations performed world-wide on a day-to-day basis, the prevention of SBI is just as important as the treatment of accident-related traumatic brain injury (TBI). The latter differs from SBI in that it is not amendable to pre-emptive therapy whereas SBI can theoretically be prevented, at least during routine elective surgery. The issue of how best to prevent cerebral edema and secondary damages in these situations are critical and deserve our research effort.
Traditionally, dexamethasone (DEXA) and other glucocorticoids (GCs) have been used as adjunctive agents during neurosurgical operations to reduce brain edema, maintain BBB integrity and minimize inflammatory responses. It has also been used in TBI patients since 1960s. However, several major studies conducted between 1979 and 2004 demonstrated that the use of GCs in severe TBI had no beneficial effect and may in fact be deleterious. Given that SBI is essentially a form of brain traumaalso, there is no logical reason why GCs should be beneficial in SBI. In this respect, our group has been investigating alternative strategies for the treatment of SBI.