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

N. Jafarian, R. Ayer, J. Eckermann, W. Tong, N. Jafarian, Richard Lee Applegate, G. Stier, R. Martin, J. Tang, John H. Zhang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationIntracerebral Hemorrhage Research: From Bench to Bedside
PublisherSpringer-Verlag Wien
Pages283-287
Number of pages5
Edition111
ISBN (Print)9783709106921
DOIs
StatePublished - 2011
Externally publishedYes

Publication series

NameActa Neurochirurgica, Supplementum
Number111
ISSN (Print)00651419
ISSN (Electronic)00016268

Keywords

  • Brain injury
  • Inflammation
  • Mucosal tolerance
  • Neuroprotection
  • TGFβ1

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Jafarian, N., Ayer, R., Eckermann, J., Tong, W., Jafarian, N., Applegate, R. L., Stier, G., Martin, R., Tang, J., & Zhang, J. H. (2011). Mucosal tolerance to brain antigens preserves endogenous TGFβ-1 and improves neurological outcomes following experimental craniotomy. In Intracerebral Hemorrhage Research: From Bench to Bedside (111 ed., pp. 283-287). (Acta Neurochirurgica, Supplementum; No. 111). Springer-Verlag Wien. https://doi.org/10.1007/978-3-7091-0693-8_47