Increased leakage of brain antigens after traumatic brain injury and effect of immune tolerance induced by cells on traumatic brain injury.
BACKGROUND
Although traumatic brain injury can lead to opening the blood-brain barrier and leaking of blood substances (including water) into brain tissue, few studies of brain antigens leaking into the blood and the pathways have been reported. Brain antigens result in damage to brain tissues by stimulating the immune system to produce anti-brain antibodies, but no treatment has been reported to reduce the production of anti-brain antibodies and protect the brain tissue. The aim of the study is to confirm the relationship between immune injury and arachnoid granulations following traumatic brain injury, and provide some new methods to inhibit the immune injury.


METHODS
In part one, methylene blue was injected into the rabbits' cisterna magna after traumatic brain injury, and concentrations of methylene blue and tumor necrosis factor (TNF)-α in blood were detected to determine the permeability of arachnoid granulations. In part two, umbilical cord mesenchymal stem cells and immature dendritic cells were injected into veins, and concentrations of interleukin 1 (IL-1), IL-10, interferon (IFN)-γ, transforming growth factor (TGF)-β, anti-brain antibodies (ABAb), and IL-12 were measured by ELISA on days 1, 3, 7, 14 and 21 after injury, and the numbers of leukocytes in the blood were counted. Twenty-one days after injury, expression of glutamate in brain tissue was determined by immunohistochemical staining, and neuronal degeneration was detected by H&E staining.


RESULTS
In part one, blood concentrations of methylene blue and TNF-α in the traumatic brain injury group were higher than in the control group (P < 0.05). Concentrations of methylene blue and TNF-α in the trauma cerebrospinal fluid (CSF) injected group were higher than in the control cerebrospinal fluid injected group (P < 0.05). In part two, concentrations of IL-1, IFN-γ, ABAb, IL-12, expression of glutamate (Glu), neuronal degeneration and number of peripheral blood leukocytes were lower in the group with cell treatment compared to the control group. IL-10 and TGF-β were elevated compared to the control group.


CONCLUSIONS
Traumatic brain injury can lead to stronger arachnoid granulations (AGs) permeability; umbilical cord mesenchymal stem cells and immature dendritic cells can induce immune tolerance and reduce inflammation and anti-brain antibodies to protect the brain tissue.
Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300070, China.
Hua
H
Yan
Hong-Wei
HW
Zhang
Qiao-Li
QL
Wu
Guo-Bin
GB
Zhang
Kui
K
Liu
Da-Shi
DS
Zhi
Zhen-Bo
ZB
Hu
Xian-Wei
XW
Zeng
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D000941:Antigens / Q000097:blood / Q000378:metabolism*; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000097:blood / Q000134:cerebrospinal fluid; D016753:Interleukin-10 / Q000097:blood / Q000134:cerebrospinal fluid; D018664:Interleukin-12 / Q000097:blood / Q000134:cerebrospinal fluid; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008751:Methylene Blue / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000097:blood / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000134:cerebrospinal fluid
D000941:Antigens; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D008751:Methylene Blue