Aquaporin-4-independent volume dynamics of astroglial endfeet during cortical spreading depression.
Brana RosicDidrik B DukefossKnut Sindre ÅbjørsbråtenWannan TangVidar JensenOle Petter OttersenRune EngerErlend A NagelhusPublished in: Glia (2019)
Cortical spreading depression (CSD) is a slowly propagating wave of depolarization of gray matter. This phenomenon is believed to underlie the migraine aura and similar waves of depolarization may exacerbate injury in a number of neurological disease states. CSD is characterized by massive ion dyshomeostasis, cell swelling, and multiphasic blood flow changes. Recently, it was shown that CSD is associated with a closure of the paravascular space (PVS), a proposed exit route for brain interstitial fluid and solutes, including excitatory and inflammatory substances that increase in the wake of CSD. The PVS closure was hypothesized to rely on swelling of astrocytic endfeet due to their high expression of aquaporin-4 (AQP4) water channels. We investigated whether CSD is associated with swelling of endfeet around penetrating arterioles in the cortex of living mice. Endfoot cross-sectional area was assessed by two-photon microscopy of mice expressing enhanced green fluorescent protein in astrocytes and related to the degree of arteriolar constriction. In anesthetized mice CSD triggered pronounced endfoot swelling that was short-lasting and coincided with the initial arteriolar constriction. Mice lacking AQP4 displayed volume changes of similar magnitude. CSD-induced endfoot swelling and arteriolar constriction also occurred in awake mice, albeit with faster kinetics than in anesthetized mice. We conclude that swelling of astrocytic endfeet is a robust event in CSD. The early onset and magnitude of the endfoot swelling is such that it may significantly delay perivascular drainage of interstitial solutes in neurological conditions where CSD plays a pathophysiological role.
Keyphrases
- high fat diet induced
- early onset
- blood flow
- cross sectional
- depressive symptoms
- stem cells
- wild type
- oxidative stress
- spinal cord injury
- mass spectrometry
- cell therapy
- spinal cord
- type diabetes
- poor prognosis
- quantum dots
- long non coding rna
- binding protein
- single cell
- drinking water
- high glucose
- physical activity
- ultrasound guided
- blood brain barrier
- deep brain stimulation
- cerebral ischemia
- protein protein