**5. Alterations in the glymphatic system: impaired brain cleaning and cooling**

The functional impairment of the paravascular system appears to be an underlying condition of the aging human brain [19], which has also been related to various CNS disorders, such as neurodegenerative disorders that are brought on by the accumulation of misfolded, prion-like proteins (e.g., Alzheimer's or amyloid angiopathy) [17, 20, 21], normal pressure hydrocephalus [19, 22, 23], post-traumatic encephalopathy [24, 25], or neuroinflammatory disorders, such as multiple sclerosis. Furthermore, the presence of the paravascular system would explain the

advantages of cisternostomy over decompressive craniectomy, in the treatment of acute brain trauma [8, 26].

Decreased intracranial compliance leads to increased intraparenchymal pressure, affecting the arterial perfusion of the brain and promoting venous congestion. On the whole, the kinetics of the fluid in the paravascular spaces is impaired. Should there be a loss of AQP4 localization, as seen in reactive astrogliosis and the aging brain, or following trauma or ischemia, or if the CSF outflow is reduced as a consequence of either CSF flow obstruction, cerebral artery pulsatility inefficiency, cerebrospinal venous insufficiency, or lymphatic disorders [27], the localized perivascular CSF recirculation may be impaired.
