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T cells but not T cells contribute to sepsis-induced white matter injury and motor abnormalities in mice

Zhang, X;Rocha-Ferreira, E;Li, T;Vontell, R;Jabin, D;Hua, S;Zhou, K;Nazmi, A;Albertsson, AM;Sobotka, K;Ek, J;Thornton, C;Hagberg, H;Mallard, C;Leavenworth, JW;Zhu, C;Wang, X;

Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (T cells and T cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) -deficient (Tcrd -/-, lacking T cells), and TCR-deficient (Tcra -/-, lacking T 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. White matter development was normal in Tcrd -/- and Tcr -/- compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcr -/- 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 Tcr -/- mice, but no such effect was observed in Tcrd -/- mice. Our results suggest that T cells but not T cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of T cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.