Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury: Laboratory investigation

Robert E. Ayer, Nazanin Jafarian, Wanqiu Chen, Richard Lee Applegate, Austin R T Colohan, John H. Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Object. Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term "surgical brain injury" (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. Methods. A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)- 1&βετα; and transforming growth factor (TGF)-&βετα;1 cytokine levels were measured 48 hours postoperatively. Results. Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein-tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1&βετα;, and increased levels of TGF&βε τα;1 following SBI. Conclusions. Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.

Original languageEnglish (US)
Pages (from-to)246-253
Number of pages8
JournalJournal of Neurosurgery
Volume116
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Mouse
  • Mucosal tolerance
  • Neuroprotection
  • Surgical brain injury
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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