The glial-lymphatic system or glymphatic system is a recently discovered fluid clearance pathway in the central nervous system. Aquaporin 4 (AQP4) water channels are part of this system. AQP4 water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal
fluid (CSF). This is an important process for the clearance of waste products from the brain. The dysfunction of the glymphatic system can lead to the accumulation of toxic substances in the brain and contribute to the pathogenesis of different neurological disorders, such as Alzheimer disease, Parkinson’s disease, etc. The glymphatic system may be impaired during bacterial meningitis as well. Pneumococcal meningitis is the most common form of community-acquired bacterial meningitis globally, associated with severe neurological sequelae.
Generoso et al. (2022) conducted an experimental study in Wistar rats, which were subjected to either pneumococcal meningitis or artificial CSF (control). Evans blue-albumin (EBA) was introduced in both groups intracisternally to trace its elimination from the CSF. Compared to the control group, the meningitis group presented a significant impairment of the glymphatic system, retaining the EBA in the CSF compartments. The authors indicate that the malfunction of the glymphatic system is manifested by the detachment of the astrocytic end feet from the blood-brain barrier vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality. This can be one of the contributing factors to the neurological sequelae developing after bacterial meningitis.
Key points:
- Glymphatic system is thought to be important for the clearance of waste products from the brain.
- The dysfunction of the glymphatic system can lead to the accumulation of toxic substances in the brain and contribute to the pathogenesis of different neurological disorders.
- Increased neuroinflammation, neuronal cell damage, and impaired neurological functions upon pneumococcal meningitis with a malfunctioning glymphatic system.
References:
- Generoso, Jaqueline S., et al. "Dysfunctional glymphatic system with disrupted aquaporin 4 expression pattern on astrocytes causes bacterial product accumulation in the CSF during pneumococcal meningitis." Mbio 13.5 (2022): e01886-22. pubmed.ncbi.nlm.nih.gov/36036510/
- Oggioni, Marco Rinaldo, and Uwe Koedel. "The Glymphatic System: a Potential Key Player in Bacterial Meningitis." Mbio 13.6 (2022): e02350-22. pubmed.ncbi.nlm.nih.gov/36286550/
Publish on behalf of the Scientific Panel on Infectious Diseases