Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury.
Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury.
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DOI：
10.3171/2011.8.jns11883
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发表时间：
2012-01
影响因子：
4.1
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Ayer RE;Jafarian N;Chen W;Applegate RL 2nd;Colohan AR;Zhang JH
颅内手术会因切口、出血、牵拉和电灼造成皮质损伤。术语“外科脑损伤”（SBI）已被开发来分类这种损伤固有的程序。神经炎症在SBI中起重要作用。传统的抗肿瘤治疗通常受到其免疫抑制副作用和CNS渗透性差的限制。这项研究使用粘膜耐受性来开发对脑髓鞘碱性蛋白（MBP）耐受的免疫系统，以便在手术破坏血脑屏障后及时和位点特异性地抑制炎症。使用使用⑶ 57小鼠的标准SBI模型。将鼻咽粘膜暴露于媒介物、卵清蛋白或MBP以形成对这些抗原的粘膜耐受性。通过超敏反应试验在体内证实了对MBP的免疫耐受性。术后48小时测量神经功能评分、脑水肿、白细胞介素（IL）-1β和转化生长因子（TGF）-β1细胞因子水平。超敏反应试验证实了对MBP的免疫耐受性的发展。髓鞘碱性蛋白耐受小鼠表现出SBI后神经损伤减轻、脑水肿减轻、IL-1β水平降低和TGFβ1水平升高。通过粘膜耐受发展术前对脑抗原的免疫耐受提供神经保护，减少脑水肿，并调节SBI后的神经炎症。
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. 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. 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. Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.