Yongtao Zheng1, Jianmin Kang2, Baolong Liu1, Weijia Fan2, Qiaoli Wu2, Kai Luo1, Hua Yan3. 1. Graduate School of Tianjin Medical University, Tianjin 300070, China. 2. Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory; Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, China. 3. Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory; Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, China. Email: yanhua20042007@sina.com.
Abstract
BACKGROUND: Many researches demonstrate that the secondary brain injury which is caused by autoimmune attack toward brain antigens plays an important role in surgical brain injury (SBI). Although traditional immunosuppression can reduce autoimmune attack, it will lower the body immunity. Immune tolerance, by contrast, not only does not lower the body immunity, but also could lighten autoimmunity. This study used thymus tolerance to develop an immune system that is tolerant to autologous cerebrospinal fluid (CSF) and autologous brain tissue so that autoimmune injury can be suppressed following the disruption of the blood-brain barrier, thereby reducing brain damage. METHODS: Eighty experimental rabbits were divided into five groups by random number table method: 16 in SBI group (group A), 16 in SBI+CSF drainage group (group B), 16 in SBI+CSF drainage+PBS injection group (group C), 16 in SBI+CSF drainage+CSF intrathymic injection group (group D), and 16 in SBI+brain homogenate intrathymic injection group (group E). Rabbits' CSF was drained in group B; was drained and injected PBS into thymus in group C; was drained and injected CSF into thymus in group D; and was injected brain homogenate in group E. Half of the rabbits in each group were phlebotomized on 1st, 3rd, 7th, and 14th days to observe the changes in IL-l, TGF-β by ELISA test, and CD4CD25 regulatory T cells ratio by flow cytometry, and in other animals brain tissues were taken on 7th day for exploring FasL expression by RT-PCR. The least significant difference (LSD) test was used to make paired comparisons; P < 0.05 was considered statistically significant. RESULTS: The levels of FasL, TGF-β, and the ratios of CD4CD25 regulatory T cells in groups D and E were apparently higher than those in other three groups (P < 0.05). Likewise, the levels of IL-1 in these two groups were lower than the other three groups (P < 0.05). Moreover, the ratios of CD4CD25 regulatory T cells and the levels of TGF-β in groups B and C were higher than those in group A, but the level of IL-1 was lower than that in group A (P < 0.05). There was no significant difference between groups B and C, and groups D and E. CONCLUSION: Thymic injection of CSF and brain homogenate may be able to reduce inflammation after SBI, so thymus immune tolerance may be a useful therapy to treat SBI.
BACKGROUND: Many researches demonstrate that the secondary brain injury which is caused by autoimmune attack toward brain antigens plays an important role in surgical brain injury (SBI). Although traditional immunosuppression can reduce autoimmune attack, it will lower the body immunity. Immune tolerance, by contrast, not only does not lower the body immunity, but also could lighten autoimmunity. This study used thymus tolerance to develop an immune system that is tolerant to autologous cerebrospinal fluid (CSF) and autologous brain tissue so that autoimmune injury can be suppressed following the disruption of the blood-brain barrier, thereby reducing brain damage. METHODS: Eighty experimental rabbits were divided into five groups by random number table method: 16 in SBI group (group A), 16 in SBI+CSF drainage group (group B), 16 in SBI+CSF drainage+PBS injection group (group C), 16 in SBI+CSF drainage+CSF intrathymic injection group (group D), and 16 in SBI+brain homogenate intrathymic injection group (group E). Rabbits' CSF was drained in group B; was drained and injected PBS into thymus in group C; was drained and injected CSF into thymus in group D; and was injected brain homogenate in group E. Half of the rabbits in each group were phlebotomized on 1st, 3rd, 7th, and 14th days to observe the changes in IL-l, TGF-β by ELISA test, and CD4CD25 regulatory T cells ratio by flow cytometry, and in other animals brain tissues were taken on 7th day for exploring FasL expression by RT-PCR. The least significant difference (LSD) test was used to make paired comparisons; P < 0.05 was considered statistically significant. RESULTS: The levels of FasL, TGF-β, and the ratios of CD4CD25 regulatory T cells in groups D and E were apparently higher than those in other three groups (P < 0.05). Likewise, the levels of IL-1 in these two groups were lower than the other three groups (P < 0.05). Moreover, the ratios of CD4CD25 regulatory T cells and the levels of TGF-β in groups B and C were higher than those in group A, but the level of IL-1 was lower than that in group A (P < 0.05). There was no significant difference between groups B and C, and groups D and E. CONCLUSION: Thymic injection of CSF and brain homogenate may be able to reduce inflammation after SBI, so thymus immune tolerance may be a useful therapy to treat SBI.