Plasma miRNA-124 and miRNA-765 as biomarkers for severe traumatic brain injury / 中华神经医学杂志

Objective To investigate the changes of plasma miRNA-124 and miRNA-765 levels in patients with severe traumatic brain injury (sTBI).Methods Thirty sTBI patients,admitted to our hospital from January 2009 to March 2010,and 24 healthy volunteers were included in the study.Quantitative RT-PCR was employed to determine the levels of miRNA-124 and miRNA-765 in the plasma and traumatic brain tissues at different time points after injury; receiver operating characteristic curve (ROC) was used to explore the potential of miRNA-124 and miRNA-765 as diagnostic TBI biomarkers.Results MiRNA-124 level dominantly increased 6 h after TBI and continued to rise 12 and 24 h,while miRNA-765 reached its peak level at 12 h after TBI in patients with sTBI,enjoying significant differences as compared with those in the matched healthy volunteers(t=2.41,P=0.001).miR-124 level (t=2.686,P=0.001) and miR-765 level (t=2.673,P=0.000) in the contusion and laceration tissues after sTBI predominantly increased as compared with those in the normal brain tissues surrounding to the contusion and laceration tissues,with significant difference.ROC curve analysis indicated that miR-124 and miR-765 were good diagnostic markers of sTBI (area under the curve:0.98 and 0.79).Conclusion Plasma-derived miR-124 and miR-765 change significantly,which could be employed as diagnostic markers for sTBI.

Increased leakage of brain antigens after traumatic brain injury and effect of immune tolerance induced by cells on traumatic brain injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Effect of erythropoietin on cognitive function in rats with traumatic brain injury / 中华神经医学杂志

Objective To evaluate the effect of erythropoietin (EPO) on cognitive function in rats with traumatic brain injury (TBI) and investigate its mechanisms. Methods Forty-eight SD rats were equally randomized into control, sham-operated, TBI and EPO+TBI groups. TBI models were established in the later 2 groups by operation and hydraulic shock. Sham-operated group received the operation only. The EPO+TBI group was injected with EPO immediately after the success of model making; the other groups were injected with saline at the same time. On the 30th d of injury, Morris water maze was employed to evaluate the cognitive function of the rats and the expression of brain-derived growth factor (BDNF) was detected by immunohistochemistry. Results In the navigation experiment, the latent period (the rats on founding the platform) in the control and sham-operated groups was significantly shorter than that in the other 2 groups (P<0.05); that in the TBI group was statistically longer than that in the EPO+TBI group (P<0.05). In the space searching experiment, the swimming times of the rats in each quadrant were significantly different (P<0.05): the control and sham-operated groups were the longest and the TBI group was the shortest of all the 4 groups. Immunohistochemistry showed that the expression of BDNF in the EPO+TBI group was significantly higher than that in the other 3 groups (P< 0.05). Conclusion TBI can damage cognitive function of the rats, while exogenous EPO may improve their memory abilities by up-regulating the expression of BDNF.

Endovascular embolization of vertibrobasilar aneurysms: report of 21 cases / 中华神经医学杂志

Objective To summarize our experience with endovascular treatment of vertibrobasilar aneurysms. Methods The clinical data of 21 patients with vertibrobasilar aneurysms admitted between October, 2003 and July, 2007 were retrospectively analyzed. All the 21 patients received endovascular embolization, of whom 11 patients had embolization with Guglielmi detachable coils (GDC), 9 had GDC embolization with Neuroform stent placement, and 1 patient was managed with covered stent placement in the parent artery. Results After the operations, 19 patients were clinically cured with good prognosis, 1 patient was severely disabled, and 1 died due to heart failure. Four patients underwent ventriculo-peritoneal shunting for postoperative hydrocephalus. Conclusions Endovascular embolization with GDC and placement of Neuroform stent and covered stent are effective options for management of vertibrobasilar aneurysms, and most of the vertibrobasilar aneurysms can be treated effectively by these approaches.

Extracellular glycerol in patients with severe traumatic brain injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the factors affecting extracellular glycerol (Gly) in patients with severe traumatic brain injury (STBI).</p><p><b>METHODS</b>Perilesional extracellular Gly and cerebral blood flow (CBF) in 53 patients with STBI were consecutively monitored. Simultaneously, the intracranial pressure (ICP) and cerebral perfusion pressure (CCP) were monitored. The hourly minimum of CCP and CBF and the hourly maximum of ICP levels were matched with the hourly Gly. Gly values were divided into several groups according to regional ICP (less than 15 mm Hg or larger than 15 mm Hg), CCP (less than 70 mm Hg or larger than 70 mm Hg), CBF (less than 50 AU or 50-150 AU) and the outcomes (death or persistent vegetative state group, severe or moderate disability group, and good recovery group).</p><p><b>RESULTS</b>In comparison with the severe or moderate disability group, the Gly concentration of the death or persistent vegetative state group increased significantly, but CBF and CCP decreased significantly. In comparison with the good recovery group, the Gly concentration of the severe or moderate disability group increased significantly, but CBF and CCP decreased significantly. The Gly concentrations in patients with ICP larger than 15 mm Hg, CCP less than 70 mm Hg and CBF less than 50 AU were respectively higher than those of patients with ICP less than 15 mm Hg, CCP larger than 70 mm Hg and 50 AU less than CBF less than 150 AU. In patients with diffuse axial injury, the mean Gly concentration was (201.17+/-55.00) micromol/L, which was significantly higher than that of the patients with epidural hematoma (n equal to 7, 73.26+/-8.37, P less than 0.05) or subdural hematoma (n equal to 9, 114.67+/-62.88, P less than 0.05), but it did not increase significantly when compared with those in patients with contusion(n equal to 24, 167.48+/-52.63).</p><p><b>CONCLUSION</b>Gly can be taken as a marker for degradation of membrane phospholipids and ischemia, which reflects the severity of primary or secondary insult.</p>

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.</p><p><b>METHODS</b>Thirty-one patients with STBI(GCS less than or equal to 8) were randomly divided into hypothermic group(Group A) and control group(Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.</p><p><b>RESULTS</b>In comparison with the control group, lactate/glucose ratio(L/G), lactate/pyruvate ratio(L/P) and glycerol(Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.</p><p><b>CONCLUSIONS</b>Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.</p>

Influence of temperature on extracellular glucose and lactate after traumatic brain injury / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the changes of extracellular glucose (Glu), lactate (Lac), and the ratio of lactate/pyruvate (L/P) in patients with traumatic brain injury under different body temperatures.</p><p><b>METHODS</b>Catheters for microdialysis were punctured into the penumbra zone of injured brain tissue (INJ), relatively normal brain tissue (NOR), and abdominal subcutaneous tissue (ABD) respectively in 51 patients to collect the fluid. The perfusion rate was 0.3 microl/min and one tube of fluid was collected for each hour. The average collection time was (67.10 +/- 18.27) hours. Concentrations of Glu, Lac, and pyruvate (Pyru) in the fluid were analyzed using CMA microdialysis analyzer. Patients were divided into 7 groups according to their rectal temperature (RT) values, which were RT < 33.0 degrees C, 33.0-33.9 degrees C, 34.0-34.9 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, 37.0-37.9 degrees C, and > or = 38.0 degrees C.</p><p><b>RESULTS</b>The concentration of Glu in ABD was significantly higher than that in the brain tissue (P < 0.05). The Glu in NOR were significantly higher and the highest in 33.0 degrees C compared with that in the INJ when RT < 36.0 degrees C (P < 0.05). The concentration of Lac in ABD was significantly lower than that in brain (P < 0.05). The Lac in NOR were much higher than that in INJ when RT < 35.0 degrees C or > or = 37.0 degrees C (P < 0.05). The ratio of L/P decreased along with the increase of body temperature (P < 0.001). The ratio of L/P significantly decreased in an order of INJ > ABD > NOR when RT was lower than 33.0 degrees C, which was changed to the order of NOR > INJ > ABD when RT was higher than 34.0 degrees C.</p><p><b>CONCLUSION</b>Treatment of hypothermia may play more protective role when RT were between 33-34 degrees C or 36-37 degrees C.</p>

Application of continuous monitoring of jugular venous oxygen saturation in the course of mild hypothermia treatment of severe traumatic brain injury / 中华创伤杂志

Objective To discuss significance of continuous monitoring of jugular venous oxygen saturation(S_(jv)O_2)in the course of mild hypothermia treatment(MHT)for severe traumatic brain injury (sTBI).Methods Intracranial pressure(ICP),S_(jv)O_2 and brain tissue pressure(P_(bt)O_2)were contin- uously monitored in 36 cases with sTBI for analyzing the correlation between S_(jv)O_2 and P_(bt)O_2.Results (1)There was negative linear correlation between P_(bt)O_2 and ICP(r=-0.978,P＜0.05),negative lin- ear correlation between S_(jv)O_2 and ICP(r=-0.947,P＜0.05)and positive linear correlation between P_(bt)O_2 and S_(jv)O_2(r=0.965,P＜0.05)within 24 hours and at 36 hours and 48 hours after injury.(2) The cases with decreased S_(jv)O_2 value had a worse outcome than those with normal S_(jv)O_2.meanwhile,the cases with abnormal increase of S_(jv)O_2 value had worse prognosis.Prognnsis was improved significantly with increase of S_(jv)O_2 in certain range(P＜0.05).Conclusion Continuous monitoring of S_(jv)O_2 can reflect the condition of hemicerebral oxygen metabolism and guide treatment and predicting outcome.