Figure 2.

Proposed mechanisms underlying dilated perivascular spaces in space crews in relation to spaceflight-associated neuro-ocular syndrome. (A) Blood volume in cerebral veins may increase as a result of a microgravity-induced decrease in cerebral venous outflow, which in turn, may lead to closure of the perivenous spaces, thereby compromising the glymphatic CSF-ISF outflow from the interstitial tissue, and resulting in diminished glymphatic clearance of metabolites from the brain. Consequently, periarterial spaces may dilate due to CSF accumulation. A reduced CSF resorption and mildly elevated ICP in microgravity may further drive CSF into the periarterial spaces, causing further fluid accumulation and PVS dilation. (B) If the cephalad venous fluid shift during spaceflight is associated with increased resistance to venous drainage from the eye, veins in the optic nerve may distend and perivenous spaces may close, resulting in diminished ocular glymphatic outflow. (C) Compromised CSF resorption and impaired cerebral venous outflow, reflected by dilated PVS, may contribute to globe flattening and optic disc edema through overflow of CSF along the optic nerve sheath and dysregulation of the ocular glymphatic system, respectively.