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

Laboratory investigation

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  • 1 Departments of Neurosurgery,
  • | 2 Anesthesiology, and
  • | 3 Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, California
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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)–1β and transforming growth factor (TGF)–β1 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-1β, and increased levels of TGFβ1 following SBI.

Conclusions

Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.

Abbreviations used in this paper:

BBB = blood-brain barrier; IL = interleukin; MBP = myelin basic protein; PBS = phosphate-buffered saline; SBI = surgical brain injury; TGF = transforming growth factor.

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