Zahra Amirkhani,1Ali Rezaeian,2,*Ali Movassagh,3Aidin Amini Sefidab,4
1. Assistant Professor, Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran. 2. Medical Student, Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran. 3. Medical Student, Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran. 4. Assistant Professor, Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran.
Introduction: The glymphatic pathway (glial lymphatic) is a fluid cleansing pathway identified in rodent brains in 2012. This pathway controls the flow of CSF to the brain along arterial vascular spaces and then to the middle brain, facilitated by Channels (AQP4). It then directs the flow path to the venous and perivascular and perineuronal spaces, eventually clearing neuropil solutions into the lymphatic drainage vessels of the meninges and cervix. The pathway consists of a para-arterial influx route for CSF to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal cord. Exchange of solutes between CSF and ISF is driven primarily by arterial pulsation and regulated during sleep by the expansion and contraction of brain extracellular space. In rodents, the glymphatic pathway is mainly active during sleep. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Glymphatic dysfunction, possibly related to the turbulent expression of AQP4, has been shown in animal models of brain injury, Alzheimer's disease and stroke.
Methods: we conducted an extensive search across electronic databases, including PubMed, MEDLINE, Embase, Google Scholar, and ResearchGate, and explored the available English-language literature. The MeSH terms were "Glymphatic system " OR " Perivascular spaces"; "Cerebrospinal fluid secretion "; "Sleep". The work of one of the researchers documents that β-amyloid concentrations in CSF follow the sleep-wake cycle in human subjects.
Results: The research group has made progress in the development of a glymphatic diagnostic test based on MRI scans. By delivering the contrast agent to cisterna magna, CSF movement can be followed in real time throughout the brain. In observations made by scientists in mice confirmed and spread the concept of the presence of a glymphatic system throughout the brain. In particular the MRI analysis showed that there was rapid flow movement in two key nodes, pituitary cavities and pineal gland. Interestingly both of these areas are involved in regulating the sleep wake cycle. Future studies with focus on the glymphatic system are expected to identify functions of convective CSF fluxes beyond removal of metabolic waste products. We have recently found that glymphatic influx can serve as a distribution system for lipids and glucose , and we speculate that glymphatic influx provides an essential route for distribution of electrolytes, macromolecules, and other larger compounds that enter the brain predominantly via the blood-CSF barrier at the choroid plexus. Likewise, the glymphatic system might serve as a path for delivery and distribution of drugs including cancer drugs within the brain.
Conclusion: Further research is needed to confirm whether certain factors that cause glymphatic flow in rodents also exist for humans. Longitudinal imaging studies that assess human CSF dynamics determine whether there is a link between reduced brain solution cleansing and the development of neurodegenerative diseases. An evaluation of glymphatic function after a stroke or brain injury can identify whether this function is associated with neurological healing. New insights into how the behavior and genetics of changing glymphatic function, and how to compensate for this function in the disease, should lead to the development of new preventive and diagnostic tools and new therapeutic goals. Although much is known about the physiological regulation of glymphatic pathway function, including the role of cerebral arterial heart rate, consciousness status, and even head position, there is currently no guided glymphatic therapy to intervene in any of these different disease processes. As a result, the main objective of future studies will be to identify a new objective to regulate or reset the CSF-ISF exchange in the glymphatic pathway, ultimately to promote improved soluble cleansing in diseases where metabolic accumulation is a prominent feature. And it should also be noted that it is an effective and investable path to future research.