The authors aim to track the distribution of human umbilical cord mesenchymal stem cells (MSCs) in large blood vessel of traumatic brain injury -rats through immunohistochemical method and small animal imaging system. After green fluorescent protein (GFP) gene was transfected into 293T cell, virus was packaged and MSCs were transfected. Mesenchymal stem cells containing GFP were transplanted into brain ventricle of rats when the infection rate reaches 95%. The immunohistochemical and small animal imaging system was used to detect the distribution of MSCs in large blood vessels of rats. Mesenchymal stem cells could be observed in large vessels with positive GFP expression 10 days after transplantation, while control groups (normal group and traumatic brain injury group) have negative GFP expression. The vascular endothelial growth factor in transplantation group was higher than that in control groups. The in vivo imaging showed obvious distribution of MSCs in the blood vessels of rats, while no MSCs could be seen in control groups. The intravascular migration and homing of MSCs could be seen in rats received MSCs transplantation, and new angiogenesis could be seen in MSCs-transplanted blood vessels.
Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2.To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen's method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test.Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes.These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.
Objective
To investigate the clinical significances of white blood cell (WBC) count at ultra-early phase (on admission) of acute traumatic brain injury (TBI).
Methods
Clinical data of 114 patients (96 males and 18 females) with acute TBI were collected. Age was 11-86 years (mean, 49 years). According to the Glasgow Coma Scale (GCS), all patients were divided into mild (13-15 points, 28 cases), moderate (9-12 points, 46 cases) and severe (3-8 points, 40 cases) groups. According to the intracranial pressure, 86 patients monitored were grouped in low- ( 30 mmHg, 28 cases) groups. All patients were divided into craniotomy (45 cases) and non-craniotomy (69 cases) groups. WBC count was recorded and compared among groups. According to the WBC count, all patients were divided into low-WBC group ( 20×109/L, 25 cases). Glasgow Outcome Scale (GOS) was compared among groups.
Results
WBC counts in mild, moderate and severe groups were (9.8±1.8)×109/L, (16.7±3.9)×109/L and (19.6±7.1 )×109/L respectively (P< 0.01). WBC counts in low-, moderate- and high-intracranial groups were (11.1±2.6)×109/L, (17.2±3.2)×109/L and (19.4±6.2)×109/L respectively (P<0.01). WBC count in craniotomy group was (18.3±6.7)×109/L, far higher than (14.5±5.3)×109/L in non-craniotomy group (P<0.01). Rate of good prognosis differed significantly among low-, moderate- and high moderate-WBC groups (χ2=28.778, P<0.01).
Conclusion
In patients with acute TBI, elevated WBC count detected immediately on admission can be used as an important parameter for assessment of injury severity, development and prognosis.
Key words:
Craniocerebral trauma; Leukocytes; Prognosis
To evaluate the effect of umbilical cord derived mesenchymal stem cells (UC-MSCs) transplantation on traumatic brain injury (TBI).UC-MSCs were isolated from human umbilical cord and TBI rat model was constructed. 30 male SD rats were randomly divided into 3 groups: control group, TBI group and MSCs transplantation group. Rats in MSCs group received the injection of a total of 1.5 Ć- 106 MSCs (25 μl) via ventricle at operated ventricular coordinates (0 at bregma, 1.5 mm at lateral, 1.1 mm at behind, 4.5 mm in depth).80% confluence of cells was formed from tissue at day 10 and the amount of CD90, CD73, CD105 positive cells increased correspondingly. In TBI model, clear hyperemia, edema and obvious infiltration of inflammatory cells in brain tissue were found. However, the manifestations were alleviated after the treatment of MSCs. In MSCs group, GFP in the brain tissue and the area around the vessels were found after the injection, while the expression levels of micro-vessel density (MVD), brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were elevated.UC-MSCs transplantation for treatment of acute TBI could effectively reduce the injury and improve the vascular reconstruction.
Objective
To investigate the protective effect of umbilical cord mesenchymal stem cells (UCMSCs) on traumatic brain injury (TBI) in rats.
Methods
Thirty healthy Sprague-Dawley rats (10 rats for each group) were randomly divided into normal control group (normal), model group (injection of saline after TBI) and UCMSCs transplantation group (injection of UCMSCs after TBI). The rats in experimental groups were sacrificed on the 10th day after UCMSCs transplantation. The percentage of UCMSCs in brain tissue was detected by flow cytometry. The pathological changes of brain tissue were observed by hematoxylin-eosin (HE) staining method. The expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) in brain tissue were measured by immunohistochemistry and immunofluorescence double staining. The neurological deficit was evaluated by neurological deficit degree.
Results
The percentage of CD90, CD73 and CD105 cells in the UCMSCs transplantation group was significantly higher than that in the model group (0.4% vs 0.1%, P<0.05). The results of HE staining showed that the brain injury of the transplanted group was alleviated compared with the model group (P<0.05). The VEGF of the brain tissue in injury area in the UCMSCs transplantation group was higher than that in the model group (P<0.05). The number of GFAP and BDNF positive cells in the UCMSCs transplantation group was higher than that in the model group (P<0.05), and the neurological deficit score was also higher than that in the model group (P<0.05).
Conclusions
UCMSCs transplantation for the treatment of TBI rats can effectively reduce the vascular damage in the injury area and promote nerve recovery.
Key words:
Umbilical cord mesenchymal stem cells; Traumatic brain injury; Vascular endothelial growth factor; Brain derived neurotrophic factor; Nerve defect score
Objective
To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on vascular endothelial growth factor(VEGF) and monocyte chemoattractant protein-1(MCP-1) of acute myocardial ischemia-reperfusion(AMI-R) injury in rats.
Methods
24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry.
Results
The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group(all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05).
Conclusion
UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.
Key words:
Human umbilical cord mesenchymal stem cells; Acute myocardial ischemia-reperfusion injury; Vascular endothelial growth factor; Monocyte chemoattractant protein-1
To investigate the protective effect and mechanism of Xingnaojing(Traditional Chinese Medicine) injection on brain injury in rats.Sixty-three healthy adult male SD rats were randomly divided into 3 groups (n = 21): sham operation group, model group, xingnaojing group. The model of traumatic brain injury model group and Xingnaojing group used the free fall impact injury method, the sham operation group underwent craniotomy, did not cause brain damage. Xingnaojing group in rats after 10 min by tail vein injection Xingnaojing injection 10 ml/(kg x d), model group and sham operation group were intravenously injected with 0.9% sodium chloride solution, three groups were administered continuously for 7 days. At administration of the seventh days compared the S-100B protein in the serum and neuro specific enolase (NSE) level, the water content of brain tissue, serum superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) content, and neurological function of rats among groups.Compared with the sham operation group, the nerve defect, brain water content, MDA, S100B protein and NSE levels were obvigusly increased in Xingnaojing group and model group; SOD, GSH-Px content decreased significantly; In Xingnaojing group nerve impairment and brain moisture were significantly lower than those of model group, the serum MDA, S-100B protein and NSE levels were significantly lower than those in the model group, the SOD, GSH-Px activity was significantly higher than that in the model group.Xingnaojing injection has protective effects on rat brain injury, and its mechanism may be related to reduce brain edema after traumatic brain injury and inhibit the reaction of oxygen free radical, protect nerve cells.