Academic Neurosurgery Unit, St George's University of London, London SW17 0RE, UK.
Neuroscience. 2010 Jul 28;168(4):1036-46. doi: 10.1016/j.neuroscience.2009.08.019. Epub 2009 Aug 12.
Brain oedema is a major clinical problem produced by CNS diseases (e.g. stroke, brain tumour, brain abscess) and systemic diseases that secondarily affect the CNS (e.g. hyponatraemia, liver failure). The swollen brain is compressed against the surrounding dura and skull, which causes the intracranial pressure to rise, leading to brain ischaemia, herniation, and ultimately death. A water channel protein, aquaporin-4 (AQP4), is found in astrocyte foot processes (blood-brain border), the glia limitans (subarachnoid cerebrospinal fluid-brain border) and ependyma (ventricular cerebrospinal fluid-brain border). Experiments using mice lacking AQP4 or alpha syntrophin (which secondarily downregulate AQP4) showed that AQP4 facilitates oedema formation in diseases causing cytotoxic (cell swelling) oedema such as cerebral ischaemia, hyponatraemia and meningitis. In contrast, AQP4 facilitates oedema elimination in diseases causing vasogenic (vessel leak) oedema and therefore AQP4 deletion aggravates brain oedema produced by brain tumour and brain abscess. AQP4 is also important in spinal cord oedema. AQP4 deletion was associated with less cord oedema and improved outcome after compression spinal cord injury in mice. Here we consider the possible routes of oedema formation and elimination in the injured cord and speculate about the role of AQP4. Finally we discuss the role of AQP4 in neuromyelitis optica (NMO), an inflammatory demyelinating disease that produces oedema in the spinal cord and optic nerves. NMO patients have circulating AQP4 IgG autoantibody, which is now used for diagnosing NMO. We speculate how NMO-IgG might produce CNS inflammation, demyelination and oedema. Since AQP4 plays a key role in the pathogenesis of CNS oedema, we conclude that AQP4 inhibitors and activators may reduce CNS oedema in many diseases.
脑水肿是由中枢神经系统疾病（如中风、脑肿瘤、脑脓肿）和全身性疾病引起的主要临床问题，这些疾病会继发性地影响中枢神经系统（如低钠血症、肝衰竭）。肿胀的大脑会压迫周围的硬脑膜和颅骨，导致颅内压升高，导致脑缺血、脑疝，最终导致死亡。水通道蛋白 4（AQP4）存在于星形胶质细胞足突（血脑边界）、胶质界膜（蛛网膜下腔脑脊髓液-脑边界）和室管膜（脑室脑脊髓液-脑边界）中。使用缺乏 AQP4 或α-联蛋白（继发性下调 AQP4）的小鼠进行的实验表明，AQP4 促进了引起细胞毒性（细胞肿胀）水肿的疾病（如脑缺血、低钠血症和脑膜炎）中水肿的形成。相比之下，AQP4 促进了引起血管源性（血管渗漏）水肿的疾病中水肿的消除，因此 AQP4 缺失加重了脑肿瘤和脑脓肿引起的脑水肿。AQP4 在脊髓水肿中也很重要。AQP4 缺失与小鼠脊髓压迫损伤后脊髓水肿减少和预后改善有关。在这里，我们考虑了损伤脊髓中水肿形成和消除的可能途径，并推测了 AQP4 的作用。最后，我们讨论了 AQP4 在视神经脊髓炎（NMO）中的作用，NMO 是一种炎症性脱髓鞘疾病，会导致脊髓和视神经水肿。NMO 患者有循环 AQP4 IgG 自身抗体，现在用于诊断 NMO。我们推测 NMO-IgG 如何产生中枢神经系统炎症、脱髓鞘和水肿。由于 AQP4 在中枢神经系统水肿的发病机制中起关键作用，我们得出结论，AQP4 抑制剂和激活剂可能会减少许多疾病中的中枢神经系统水肿。
