Alcohol promotes waste clearance in the CNS via brain vascular reactivity

Now we just need to know what low dose alcohol means.  Removal of entangled proteins sounds important in preventing Alzheimers. But I know nothing, I'm not medically trained. Can your doctor decipher the amount of alcohol needed for these results?

Alcohol promotes waste clearance in the CNS via brain vascular reactivity

Author links open overlay panelYimingCheng^aXingleiLiu^bXiaotangMa^aRicardoGarcia^aKevinBelfield^bJamesHaorah^a

https://doi.org/10.1016/j.freeradbiomed.2019.07.029Get rights and content

Highlights

•

Waste metabolites like beta-amyloid protein in the brain are unable to clear out by the conventional CSF clearance path and due to the absence of lymphatic system in the CNS.

•

As such waste metabolites are seen to diffuse to perivascular-perivenous space from interstitial fluid and from CSF-subarachnoid flow.

•

Low dose alcohol promotes the dynamic movement pattern of these waste metabolites towards perivascular-perivenous space for clearance.

•

Alcohol-elicited eNOS activation and NO production regulates the clearance path through arterial vessel dilation.

Abstract

The efficient clearance of the interstitial waste metabolites is essential for the normal maintenance of brain homeostasis. The brain lacks the lymphatic clearance system. Thus, the drainage of waste metabolites in the brain is dependent on a slow flow of cerebrospinal fluid (CSF) system. Glymphatic system claims the direct bulk flow transport of small size water-soluble waste metabolites into to the perivenous space by aquaporin-4 water channels of the astrocyte end-feet, but it did not address the diffusive clearance of large size waste metabolites. Here, we addressed the clearance mechanisms of large size waste metabolites from interstitial fluid to perivascular space as well as from CSF subarachnoid into perivascular space via the paravascular drainage. A low dose ethanol acting as a potent vasodilator promotes the dynamic clearance of waste metabolites through this perivascular-perivenous drainage path. We observed that ethanol-induced increased in vascular endothelial and smooth muscle cell reactivity regulated the enhanced clearance of metabolites. Here, activation of endothelial specific nitric oxide synthase (eNOS) by ethanol and generation of vasodilator nitric oxide mediates the interactive reactivity of endothelial-smooth muscle cells and subsequent diffusion of the CNS waste metabolites towards perivascular space. Detection of tracer dye (waste metabolite) in the perivenous space and in the blood samples further confirmed the improved clearance of waste metabolites through this unraveled interstitial-perivascular-perivenous clearance path. Our results suggest that alcohol intake at low-dose levels may promote clearance of neurological disease associated entangled proteins.

Graphical abstract

(A) Arrows (orange) indicate the CSF subarachnoid flow and perivascular-perivenous clearance path (black) of large size waste metabolites (red dots) in neurodegenerative brain. Waste metabolites like β-amyloid proteins are aggregated more inside the interstitial space due to the lack of lymphatic system in the brain. Less metabolite are drained into the CSF flows due to less vessel dilative reactivity. (B) Neurodegenerative brain in the presence of low dose alcohol. Dilative arterial vessel reactivity promotes the dynamic movement of large size waste metabolites from interstitial fluid to perivascular space and from interstitial-CSF subarachnoid to perivascular space. Reactivity of endothelial and smooth muscle cells in arteries is mediated by alcohol-elicited eNOS activation and NO production.

1. Download high-res image (479KB)
2. Download full-size image

Keywords

CNS clearance

CSF

Perivascular space

Alcohol

eNOS

Research data for this article

Data not available / Data will be made available on request

About research data