Aquaporin-4 and brain edema - PubMed (original) (raw)

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Aquaporin-4 and brain edema

Marios C Papadopoulos et al. Pediatr Nephrol. 2007 Jun.

Abstract

Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury.

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Figures

Fig. 1

Fig. 1

Mechanisms of aquaporin (AQP) function outside the brain. a Reduced water permeability in glandular epithelium impairs active, near-isosmolar fluid transport by slowing osmotic water transport into the acinar lumen, producing hypertonic secretion. b Reduced transepithelial water permeability in kidney collecting duct impairs urinary concentrating ability by preventing osmotic equilibration of luminal fluid. c AQP-facilitated water entry into protruding lamellipodia, accounting for AQP-dependent cell migration. d Reduced steady-state glycerol content in epidermis and stratum corneum following AQP3 deletion, accounting for reduced skin hydration in AQP3 deficiency. e Impaired AQP7-dependent glycerol escape from adipocytes, resulting in intracellular glycerol accumulation and increased triglyceride content accounting for progressive adipocyte hypertrophy in AQP7 deficiency

Fig. 2

Fig. 2

Routes of water exit from the brain in brain edema. In both cytotoxic and vasogenic types of brain edema, excess fluid is eliminated through aquaporin-4 (AQP4) rich barriers: a The glia limitans externa into the subarachnoid space; b the blood–brain barrier into the bloodstream; c the glia limitans interna and ependyma into the ventricles

Fig. 3

Fig. 3

Aquaporin-4 (AQP4) null mice are protected from hyponatremic brain swelling. a Improved survival of AQP4-null (AQP4−/−) mice compared with wild-type (AQP4+/+) mice following water intoxication produced by injecting 0.2 ml/g body weight intraperitoneally. b Transmission electron micrograph showing edematous cerebral cortex at 30 min. Note the swollen astrocytic foot process in brains from AQP4+/+ (black arrows) and AQP4−/− (white arrows) mice. Scale bar represents 3 μm

Fig. 4

Fig. 4

Aquaporin-4 (AQP4) deletion worsens ventricular enlargement in hydrocephalus. a Coronal brain sections showing ventricle size in a normal mouse (top) and in a mouse with obstructive hydrocephalus (bottom) produced by kaolin injection into the cisterna magna. b Lateral ventricle size in wild-type (AQP4+/+) and AQP4-null (AQP4−/−) mice following kaolin injection

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