BACKGROUNDAlthough 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.

METHODSIn 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.

RESULTSIn 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.

CONCLUSIONSTraumatic 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.

Adipocytes ; cytology ; Animals ; Antigens ; blood ; metabolism ; Brain Injuries ; blood ; cerebrospinal fluid ; metabolism ; Cell Differentiation ; physiology ; Cells, Cultured ; Dendritic Cells ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Interleukin-1 ; blood ; cerebrospinal fluid ; Interleukin-10 ; blood ; cerebrospinal fluid ; Interleukin-12 ; blood ; cerebrospinal fluid ; Mesenchymal Stromal Cells ; cytology ; Methylene Blue ; metabolism ; Osteoblasts ; cytology ; Rabbits ; Transforming Growth Factor beta ; blood ; cerebrospinal fluid ; Tumor Necrosis Factor-alpha ; blood ; cerebrospinal fluid

Subarachnoid hemorrhage (SAH) induces an inflammatory reaction and may lead to ischemic brain damage. The pathogenesis of brain dysfunction and delayed ischemic symptoms remain difficult to understand despite extensive surveys of such reactions. Cytokine production in the central nervous system following SAH and its relation with clinical outcome have hardly been studied. This study was aimed to determine whether the levels of IL-1 beta, IL-6 and TNF-alpha in the initial cerebrospinal fluid would increase following aneurysmal SAH, and be related with development of delayed ischemic deficit and clinical outcome. Nineteen patients suffering from aneurysmal SAH and 12 control volunteers were the subjects in this study. Cerebrospinal fluid samples were obtained on admission and the levels of each cytokine were determined with enzyme-linked immunosorbent assay. Patients with aneurysmal subarachnoid hemorrhage showed elevated levels of IL-1 beta, and TNF-alpha on admission. The patients with poor neurological status showed high levels of IL-1 beta, and IL-6. The patients who developed delayed ischemic deficit had high level of IL-6. We suggest that elevated level of IL-6 in cerebrospinal fluid of patients with aneurysmal SAH on admission can predict the high risk of delayed ischemic deficit.
Adult ; Aged ; Brain Ischemia/*cerebrospinal fluid/*diagnosis/immunology ; Cytokines/*cerebrospinal fluid ; Female ; Glasgow Outcome Scale ; Human ; Interleukin-1/cerebrospinal fluid ; Interleukin-6/cerebrospinal fluid ; Male ; Middle Age ; Predictive Value of Tests ; Subarachnoid Hemorrhage/*cerebrospinal fluid/*diagnosis/immunology ; Tumor Necrosis Factor/cerebrospinal fluid