First Author | Zhang X | Year | 2017 |
Journal | J Neuroinflammation | Volume | 14 |
Issue | 1 | Pages | 255 |
PubMed ID | 29262837 | Mgi Jnum | J:271908 |
Mgi Id | MGI:6282289 | Doi | 10.1186/s12974-017-1029-9 |
Citation | Zhang X, et al. (2017) gammadeltaT cells but not alphabetaT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice. J Neuroinflammation 14(1):255 |
abstractText | BACKGROUND: Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. METHODS: In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (alphabetaT cells and gammadeltaT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) delta-deficient (Tcrd (-/-), lacking gammadeltaT cells), and TCRalpha-deficient (Tcra (-/-), lacking alphabetaT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. RESULTS: White matter development was normal in Tcrd (-/-) and Tcralpha (-/-) compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcralpha (-/-) mice, but not in the Tcrd (-/-) mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcralpha (-/-) mice, but no such effect was observed in Tcrd (-/-) mice. CONCLUSIONS: Our results suggest that gammadeltaT cells but not alphabetaT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of gammadeltaT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury. |