title: Mucosal tolerance to brain antigens preserves endogenous TGFβ-1 and improves neurological outcomes following experimental craniotomy.
abstract: 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.
authors: Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA, USA.
authors: N
authors: N
authors: Jafarian
authors: R
authors: R
authors: Ayer
authors: J
authors: J
authors: Eckermann
authors: W
authors: W
authors: Tong
authors: N
authors: N
authors: Jafarian
authors: R L
authors: RL
authors: Applegate
authors: G
authors: G
authors: Stier
authors: R
authors: R
authors: Martin
authors: J
authors: J
authors: Tang
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D003399:Craniotomy / Q000009:adverse effects*; D004195:Disease Models, Animal; D004361:Drug Tolerance / Q000276:immunology; D007249:Inflammation / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009460:Neurologic Examination; D010047:Ovalbumin / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004676:Myelin Basic Protein; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin