Mucosal tolerance to brain antigens preserves endogenous TGFβ-1 and improves neurological outcomes following experimental craniotomy.

Intracranial surgery causes brain damage from cortical incisions, intraoperative hemorrhage, retraction, and electrocautery; collectively these injuries have recently been coined surgical brain injury (SBI). Inflammation following SBI contributes to neuronal damage. This study develops T-cells that are immunologically tolerant to brain antigen via the exposure of myelin basic protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to the site of corticotomy, secrete immunosuppressive cytokines, such as TGFβ1, reduce inflammation, and improve neurological outcomes following SBI. A standard model for SBI was used for this experiment. C57 mice were divided into six groups: SHAM + Vehicle, SHAM + Ovalbumin, SHAM + MBP, SBI + Vehicle, SBI + OVA, and SBI + MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was performed prior to SBI. Neurological scores and TBFβ1 cytokine levels were measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction in neurological score. Animals tolerized to MBP (SBI + MBP) had better postoperative neurological scores than SBI + Vehicle and SBI + OVA. SBI inhibited the cerebral expression TGFβ1 in PBS and OVA treated groups, whereas MBP treated-animals preserved preoperative levels. Mucosal tolerance to MBP leads to significant improvement in neurological outcome that is associated with the preservation of endogenous levels of brain TGFβ1.