Intraparenchymal Application of Mature B Lymphocytes Improves Structural and Functional Outcome after Contusion Traumatic Brain Injury

Abstract

Cerebral contusion causes neurological dysfunction mediated in part by inflammatory responses to injury. B lymphocytes are dynamic regulators of the immune system that have not been systematically studied in traumatic brain injury (TBI). We showed previously that topically applied mature B cells have immunomodulatory properties and strongly promote tissue regeneration, including cutaneous nerve growth, in acute and chronic skin wounds. Using a mouse controlled cortical impact (CCI) model, we assessed a possible beneficial role of exogenously applied B cells on histopathological and functional outcome after TBI. Mice were injected intraparenchymally at the lesion site with 2 × 10⁶ mature naïve syngeneic splenic B cells, then subjected to CCI. Control CCI mice received equal numbers of T cells or saline, and sham-injured mice (craniotomy only) were given B cells or saline. Sham-injured groups performed similarly in motor and learning tests. Injured mice administered B cells showed significantly improved post-injury rotarod, Y maze, and Morris water maze (MWM) performance compared with saline- or T-cell-treated CCI groups. Moreover, lesion volume in mice treated with B cells was significantly reduced by 40% at 35 days post-TBI compared with saline and T cell controls, and astrogliosis and microglial activation were decreased. In vivo tracking of exogenous B cells showed that they have a limited life span of approximately 14 days in situ and do not appear to proliferate. The data suggest proof of principle that local administration of B lymphocytes may represent a therapeutic option for treatment of cerebral contusion, especially when clinical management involves procedures that allow access to the injury site.