Leukocyte infiltration and trafficking during in-flammatory states in the newborn mouse brain
Abstract: Objective: Inflammation is associated with higher incidence of perinatal brain injury. To better understand the mechanisms behind these injuries, we have studied the immune cell trafficking into the central nervous system (CNS) through the choroid plexus (CP) in the newborn. Meth-ods: Inflammation was induced in newborn mice using two different toll-like receptor ago-nists: PAM3CSK4 (PAM) and lipopolysaccharide (LPS). The number of leukocytes in the cer-ebrospinal fluid (CSF) was estimated at 6, 14, 24 and 48 hours after agonist injection. The location and number of white blood cells present in the brain and CP at 14 hours after agonist treatment was determined by immunofluorescence. Finally, the tight junction proteins in the CP were studied by immunofluorescence. Results: The number of leukocytes in the CSF of PAM treated animals peaked at 14 h, and was significantly higher than in the LPS and control animals. In addition, the number of leukocytes in the CP and the brain was significantly high-er in PAM injected animals than in the control and LPS groups. In the PAM treated animals, large clusters of cells were frequently seen in the meningeal border but also in blood vessels and some in the brain parenchyma. There were no visible changes in the staining pattern of the tight junction proteins in the CP. Interpretation: After peripheral stimulation of TLR-1/2, leu-kocytes may be migrating through the CP, but they may also be moving through the other bar-riers of the CNS.
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