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

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Intracerebral Hemorrhage Research

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 111))

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.

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Acknowledgment

This study was partially supported by NIH NS053407 to J.H. Zhang and NS060936 to J. Tang.

Conflict of interest statement We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    N. Jafarian, R. L. Applegate II, G. Stier, R. Martin & John H. Zhang

  2. Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA, USA

    R. Ayer, J. Eckermann & John H. Zhang

  3. Department of Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, CA, USA

    W. Tong, N. Jafarian, J. Tang & John H. Zhang

  4. Department of Neurosurgery, Loma Linda University Medical Centre, 11234 Anderson Street, Room 2562B, Loma Linda, CA, USA

    John H. Zhang

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  1. N. Jafarian
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  2. R. Ayer
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  3. J. Eckermann
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  4. W. Tong
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  9. J. Tang
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  10. John H. Zhang
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Correspondence to John H. Zhang .

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Editors and Affiliations

  1. , Neurosurgery, Physiology, Loma Linda University, Campus Street 11041, Loma Linda, 92530, USA

    John Zhang

  2. School of Medicine, Dept. Neurosurgery, Loma Linda University, Anderson St. 11234, Loma Linda, 92354, California, USA

    Austin Colohan

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© 2011 Springer-Verlag/Wien

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Jafarian, N. et al. (2011). Mucosal Tolerance to Brain Antigens Preserves Endogenous TGFβ-1 and Improves Neurological Outcomes Following Experimental Craniotomy. In: Zhang, J., Colohan, A. (eds) Intracerebral Hemorrhage Research. Acta Neurochirurgica Supplementum, vol 111. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0693-8_47

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  • DOI: https://doi.org/10.1007/978-3-7091-0693-8_47

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  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0692-1

  • Online ISBN: 978-3-7091-0693-8

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