Macrostructural, microstructural, and cellular effects of neuroinflammation on the mouse brain

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Neuroinflammation is linked to brain atrophy, cognitive decline, and neurodegenerative diseases.
• Understanding the brain's response to inflammation is crucial for developing treatments.

Purpose of the Study:

• To investigate the macrostructural, microstructural, and cellular effects of lipopolysaccharide (LPS)-induced neuroinflammation in the mouse brain.
• To identify specific brain regions and neuronal subtypes affected by neuroinflammation.

Main Methods:

• Systemic lipopolysaccharide (LPS) administration in a mouse model.
• Whole-brain two-photon microscopy, multiparametric magnetic resonance imaging (MRI).
• In silico transcriptomics analysis.

Main Results:

• LPS increased microglial soma size, indicating proinflammatory transformation.
• In vivo volumetric increases in brain regions (suggesting edema) spared the cerebral cortex.
• Ex vivo analysis revealed microstructural alterations (reduced fractional anisotropy and magnetization transfer ratio) in the cerebral cortex, affecting specific neuronal subtypes and synapses.

Conclusions:

• LPS-induced neuroinflammation causes brain edema and microstructural changes, primarily impacting the cerebral cortex.
• These alterations may involve specific inhibitory and excitatory neurons and their synapses.
• The findings provide insights into the neuropathology of inflammatory conditions.