Background
Microglia are resident innate immune cells in the brain, and activation of these myeloid cells
Conclusions
Systemic administration of LPS produced microglia activation in the CC and resultant functional abnormalities that were attenuated by an anti-inflammatory agent minocycline.
Methods
Twenty-four SD rats were divided randomly into three groups and intra-peritoneally injected daily with saline, LPS, and LPS + minocycline, respectively. All animals were subject to MRI tests 6 days post-injection. The animals were then sacrificed to harvest the CC tissues for electrophysiology, western blotting, and immunocytochemistry. One-way ANOVA with Tukey's post-test of all pair of columns was employed statistical analyses.
Results
Systemic administration of LPS produced microglial activation in the CC as illustrated by Iba-1 immunofluorescent staining. We observed that a large number of Iba-1-positive microglial cells were hyper-ramified with hypertrophic somata or even amoeba like in the LPS-treated animals, and such changes were significantly reduced by co-administration of minocycline. Electrophysiological recordings of axonal compound action potential (CAP) in the brain slices contained the CC revealed an impairment on the CC functionality as detected by a reduction in CAP magnitude. Such an impairment was supported by a reduction of fast axonal transportation evidenced by β-amyloid precursor protein accumulation. These alterations were attenuated by minocycline, demonstrating minocycline reduction of microglia-mediated interruption of white matter integrity and function in the CC. Conclusions: Systemic administration of LPS produced microglia activation in the CC and resultant functional abnormalities that were attenuated by an anti-inflammatory agent minocycline.