Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats

• 来源期刊: 生物医学研究杂志（英文版）
• 学科: 医学
• 年，卷（期）: 2018,（2）
• 页码范围: 136-144
• 页数: 9页
• 分类号: R34
• 语种: 英文

摘要

Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke.Axon degeneration and demyelination can activate microglia;however,it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury.Rat corpus callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS + Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4) antagonist.Functional changes reflected by the change ofaxon compound action potentials (CAPs) and the accumulation of β-amyloid precursor protein (β-APP) in CC nerve fibers.Microglia activation was monitored by ionized calcium binding adaptor-1 immunofluorescent stain,based on well-established morphological criteria and paralleled proportional area measurement.Input-output (I/O) curves of CAPs in response to increased stimuli were significantly downshifted in a dose-dependent manner in LPS (0.2,0.5 and 1.0 μg/mL)-treated slices,implying that axons neurophysiological function was undermined.LPS caused significant β-APP accumulation in CC tissues,reflecting the deterioration of fast axon transport.LPS-induced I/O curve downshift and β-APP accumulation were significantly reversed by the pre-treatment or co-incubation with RS-LPS.RS-LPS alone did not change the I/O curve.The degree of malfunction was correlated with microglia activation,as was shown by the measurements of proportional areas.Function of CC nerve fibers was evidently impaired by microglia activation and reversed by a TLP-4 antagonist,suggesting that the TLP-4 pathway lead to microglia activation.