Acute systemic LPS-exposure impairs perivascular CSF distribution in mice

Area of Science:

• Neuroscience
• Immunology
• Physiology

Background:

• Cerebrospinal fluid (CSF) and interstitial fluid exchange is vital for brain waste clearance.
• The sleep-dependent glymphatic system, reliant on arterial pulsatility and astrocytic aquaporin-4 (AQP4), facilitates brain clearance.
• Impaired glymphatic function is linked to neurodegenerative diseases, prompting investigation into inflammation's effects.

Purpose of the Study:

• To investigate the impact of acute inflammation, induced by lipopolysaccharide (LPS), on the brain's glymphatic system.
• To measure the effect of LPS on perivascular CSF distribution as an indicator of glymphatic function.

Main Methods:

• C57bl/6 mice received LPS injections (1 mg/kg i.p.).
• CSF tracers were injected into the cisterna magna and imaged in fixed brains and vibratome-cut slices.
• Physiological parameters, including cytokines, glial and BBB markers, cerebral blood flow, and AQP4 polarization, were assessed.

Main Results:

• LPS injections significantly reduced perivascular CSF tracer flow and parenchymal penetration.
• No significant changes were observed in AQP4 polarization, cytokines, astroglial markers, BBB permeability, cerebral blood flow, or respiration.
• LPS administration elevated cortical Iba1+ area and heart rate.

Conclusions:

• Acute exposure to LPS causes a significant decrease in perivascular CSF distribution.
• These findings contribute to understanding the role of systemic inflammation in brain clearance mechanisms.