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手术性颅脑损伤后，脑抗原的术前黏膜耐受和神经保护免疫应答。

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

机构信息

Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, California 92354, USA.

出版信息

J Neurosurg. 2012 Jan;116(1):246-53. doi: 10.3171/2011.8.JNS11883. Epub 2011 Oct 21.

DOI:10.3171/2011.8.JNS11883
PMID:22017304
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4373079/
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)-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.

摘要

目的

颅内手术会因切口、出血、牵拉和电灼而导致皮质损伤。“手术性脑损伤（SBI）”这一术语的出现是为了将手术过程中固有损伤进行分类。神经炎症在 SBI 中起着重要作用。传统的抗炎疗法往往受到其免疫抑制副作用和对中枢神经系统（CNS）穿透性差的限制。本研究利用黏膜耐受来开发一种对脑髓鞘碱性蛋白（MBP）具有耐受性的免疫系统，以便在血脑屏障手术后及时、特异性地抑制炎症。

方法

采用 CD57 小鼠的标准 SBI 模型。通过鼻黏膜暴露于载体、卵清蛋白或 MBP 来诱导对这些抗原的黏膜耐受。通过过敏测试在体内确认 MBP 的免疫耐受。术后 48 小时测量神经功能评分、脑水肿以及白细胞介素（IL）-1β和转化生长因子（TGF）-β1 细胞因子水平。

结果

过敏测试证实了对 MBP 的免疫耐受的发展。MBP 耐受小鼠在 SBI 后表现出神经损伤减轻、脑水肿减少、IL-1β水平降低和 TGFβ1 水平升高。

结论

通过黏膜耐受预先诱导对脑抗原的免疫耐受可提供神经保护，减轻 SBI 后的脑水肿，并调节神经炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/e46795347d6c/nihms672291f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/15bed4599aa5/nihms672291f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/95d66644766f/nihms672291f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/497e5d59a19e/nihms672291f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/e46795347d6c/nihms672291f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/15bed4599aa5/nihms672291f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/95d66644766f/nihms672291f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/497e5d59a19e/nihms672291f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7324/4373079/e46795347d6c/nihms672291f4.jpg

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