Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China.
Department of Neurosurgery, Hebei Yanda Hospital, Langfang, China.
Front Immunol. 2022 Jul 6;13:928343. doi: 10.3389/fimmu.2022.928343. eCollection 2022.
Craniocerebral trauma is caused by external forces that can have detrimental effects on the vasculature and adjacent nerve cells at the site. After the mechanical and structural primary injury, a complex series of secondary cascades of injury exacerbates brain damage and cognitive dysfunction following mechanical and structural primary injury. Disruption of the blood-brain barrier and exposure of brain proteins following craniocerebral trauma, recognition by the immune system triggering autoimmune attack, and excessive secondary inflammatory responses causing malignant brain swelling, cerebral edema, and subsequent brain cell apoptosis provide a new direction for the suppression of brain inflammatory responses in the treatment of craniocerebral trauma. We observed that CD4T/CD8T in peripheral blood T cells of craniocerebral trauma rats were significantly higher than those of normal rats, and the ratio of CD4CD25Foxp3 (Foxp3)Regulatory T cell (Treg) was significantly lower than that of normal rats and caused increased secondary inflammation. We constructed a rat model of post-surgical brain injury and orally administered brain protein combined with probiotics, which was observed to significantly reduce CD4T/CD8T and induce T-cell differentiation into CD4CD25Foxp3Treg, thus, reducing secondary inflammatory responses following craniocerebral trauma. However, collecting intestinal stool and small intestinal tissues for broad target metabolomics, 16s rRNA bacteriomics, and the combined analysis of intestinal tissue proteomics revealed that oral administration of brain protein combined with probiotics activates glycerophospholipid and vitamin B6 metabolic pathways to promote the production of CD4CD25Foxp3Treg. Therefore, we propose the novel idea that oral administration of brain protein combined with probiotics can induce immune tolerance by increasing Treg differentiation, thus, reducing secondary inflammatory injury following craniocerebral trauma.
颅脑损伤是由外力引起的，可对损伤部位的血管和邻近神经细胞产生有害影响。在机械和结构的原发性损伤之后，一系列复杂的继发性损伤级联反应加剧了机械和结构的原发性损伤后的脑损伤和认知功能障碍。颅脑损伤后血脑屏障的破坏和脑蛋白的暴露，被免疫系统识别触发自身免疫攻击，以及过度的继发性炎症反应导致恶性脑肿胀、脑水肿和随后的脑细胞凋亡，为抑制颅脑创伤治疗中的脑炎症反应提供了新的方向。我们观察到，颅脑损伤大鼠外周血 T 细胞中的 CD4T/CD8T 明显高于正常大鼠，且 CD4CD25Foxp3（Foxp3）调节性 T 细胞（Treg）的比例明显低于正常大鼠，导致继发性炎症反应增加。我们构建了手术后脑损伤大鼠模型，并经口给予脑蛋白联合益生菌，观察到其明显降低了 CD4T/CD8T，并诱导 T 细胞分化为 CD4CD25Foxp3Treg，从而减轻颅脑损伤后的继发性炎症反应。然而，通过广泛的靶向代谢组学、16s rRNA 细菌组学以及肠组织蛋白质组学的联合分析，收集肠道粪便和小肠组织，我们发现口服脑蛋白联合益生菌可激活甘油磷脂和维生素 B6 代谢途径，促进 CD4CD25Foxp3Treg 的产生。因此，我们提出了一个新的观点，即口服脑蛋白联合益生菌可通过增加 Treg 分化来诱导免疫耐受，从而减轻颅脑创伤后的继发性炎症损伤。
