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Updated: Jan 20, 2026
Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics
Published on: November 30, 2012
Lipopolysaccharide disrupts the cochlear blood-labyrinth barrier by activating perivascular resident macrophages and
Ying Jiang1, Jie Zhang2, Yufang Rao1
1Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Objective:
To determine the distribution of perivascularresident macrophages (PVMs) in BLB and their relationship with capillaries, and to explore the possible mechanisms responsible for lipopolysaccharide (LPS)-induced activation of PVMs and the breakdown of BLB.
Methods:
Adult Balb/c mice were either trans-tympanically injected with LPS, or mock-treated. Auditory brainstem response was tested before and 48 h after treatments. Distribution of pericytes, PVMs and capillaries was analyzed by immunohistochemical staining, and BLB permeability was estimated by FITC-dextran leakage assay. Ultrastructure of stria vascularis was examined by transmission electron microscope. Protein and mRNA level of matrix metallopeptidase 9 (MMP-9), zona occludens-1 (ZO-1), interleukin-33 (IL-33) and its receptor suppression of tumorigenicity 2 (ST2) was measured by IHC and qRT-PCR.
Results:
Unlike pericytes that surround one capillary, PVMs branched to connect with more than one capillary. LPS caused hearing loss in mice. Following LPS challenge, cochleae showed vascular leakage in stria vascularis, and PVMs presented morphological changes including reduced contact with capillaries. TEM revealed a reduced number of tight junction contact points between endothelial cells and a wider space between PVMs, pericytes and endothelial cells. The mRNA and protein levels of MMP-9 and ST2 in stria vascularis were up-regulated, while ZO-1 were down-regulated after exposure to LPS.
Conclusions:
Our results suggest that PVMs may play a more significant role than pericytes in maintaining the integrity of BLB. Our findings also reveal a possible mechanism contributing to LPS-induced activation of PVMs, breakdown of BLB and hearing loss.
Insights
Perivascular resident macrophages (PVMs) are crucial for blood-labyrinth barrier (BLB) integrity. Lipopolysaccharide (LPS) disrupts BLB by altering PVMs, leading to hearing loss.
Area of Science:
- Neuroscience
- Immunology
- Otolaryngology
Background:
- The blood-labyrinth barrier (BLB) protects the inner ear.
- Perivascular resident macrophages (PVMs) are immune cells within the inner ear vasculature.
- The role of PVMs in BLB integrity and their response to inflammatory stimuli like lipopolysaccharide (LPS) are not fully understood.
Purpose of the Study:
- To investigate the distribution and function of PVMs in the BLB.
- To explore the mechanisms underlying LPS-induced PVM activation and BLB breakdown.
- To correlate these changes with hearing loss.
Main Methods:
- Adult Balb/c mice were treated with LPS or a control.
- Auditory brainstem response was measured to assess hearing.
- Immunohistochemistry and FITC-dextran leakage assays were used to analyze PVMs, capillaries, and BLB permeability.
- Transmission electron microscopy examined the ultrastructure of the stria vascularis.
- MMP-9, ZO-1, IL-33, and ST2 expression was quantified via IHC and qRT-PCR.
Main Results:
- PVMs exhibit a distinct branching pattern connecting multiple capillaries, unlike pericytes.
- LPS administration induced hearing loss, vascular leakage in the stria vascularis, and morphological changes in PVMs.
- Tight junctions were compromised, evidenced by reduced contact points and increased intercellular space.
- MMP-9 and ST2 expression increased, while ZO-1 expression decreased post-LPS exposure.
Conclusions:
- PVMs play a more critical role than pericytes in maintaining BLB integrity.
- LPS triggers PVM activation and BLB breakdown through specific molecular pathways, contributing to hearing impairment.
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