Mucosal Tolerance to Brain Antigens Preserves Endogenous TGFβ-1 and Improves Neurological Outcomes Following Experimental Craniotomy

• DOI: 10.1007/978-3-7091-0693-8_47
• Publication Date: 2011-06-18T00:18:56Z
• Authors: N. Jafarian; R. Ayer; J. Eckermann; W. Tong; N. Jafarian; R. L. Applegate; G. Stier; R. Martin; J. Tang; John H. Zhang
• Keywords: Inflammation; Neurologic Examination; Analysis of Variance; Mucous Membrane; Ovalbumin; Brain; Myelin Basic Protein; Drug Tolerance; 3. Good health; Mice, Inbred C57BL; Transforming Growth Factor beta1; Disease Models, Animal; Mice; Treatment Outcome; Brain Injuries; Animals; 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.