Aquaporin-4 in brain and spinal cord oedema

Aug 18, 2009Neuroscience

Role of Aquaporin-4 in Brain and Spinal Cord Swelling

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

AQP4 deletion was associated with less cord oedema and improved outcomes after compression spinal cord injury in mice.

Brain oedema is linked to various CNS diseases and can lead to severe complications, including death.
AQP4 is involved in the formation of cytotoxic oedema in conditions like cerebral ischaemia and meningitis.
In contrast, AQP4 aids in the elimination of vasogenic oedema, with its absence worsening conditions like brain tumours and abscesses.
The role of AQP4 extends to spinal cord oedema, where its deletion can lead to reduced swelling.
Circulating AQP4 IgG autoantibody is used as a diagnostic marker for neuromyelitis optica (NMO), which causes CNS inflammation and demyelination.
AQP4 inhibitors and activators may have potential therapeutic effects on CNS oedema across various diseases.

AI simplified

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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Aquaporin-4 in brain and spinal cord oedema

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief