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.