This research was to study the regulation of intravenous administration of human umbilical cord blood mesenchymal stem cells (HUCBMSCs) on secretion of neural specific protein in rats after traumatic brain injury (TBI), and to explore its mechanisms promoting the recovery of neurological function. The TBI models of rats were established. We then injected HUCBMSCs, labelled by Brdu (5-bromo-2-deoxyuridine), into the TBI rats via the tail vein using modified Feeney free-falling method. The levels of neural biochemical indicators (serum S100βprotein, NSE, LDH, CK) of rats were detected in shamed group, injury group and HUCBMSCs-transplanted group. And the morphological changes of brain tissue of rats in the three groups were observed by using HE staining under light microscope. During the whole experiment no immunosuppressant was used for the four groups. From the research, transplant-related death of the rats was not found in transplantation group. In the injury group, rises were found in contents of serum S100βprotein, NSE, LDH, CK in the early stage after the rats were injured, which were much higher than those in shamed group at correspondent time point(P < 0.01). In HUCBMSCs-transplanted group, although these biochemistry indexes were found rising for a short period in the early stage, along with the time, these indexes were obviously lower than in those injury group (P < 0.05). Under light microscopy pathological changes of rats in HUCBMSCs-transplanted group were much slighter than those in injury group. It was well concluded that in the situation of no immuno-suppressants, the intravenous-injected HUCBMSCs could reduce the secretion of serum S100βprotein, NSE, LDH, CK, promote the repair of tissue injury effectively, and promote the functional recovery of neurons.
ObjectiveTo investigate the possibility and effect of chitosan porous scaffolds combined with bone marrow mesenchymal stem cells (BMSCs) in repair of neurological deficit after traumatic brain injury (TBI) in rats.MethodsBMSCs were isolated, cultured, and passaged by the method of bone marrow adherent culture. The 3rd generation BMSCs were identified by the CD29 and CD45 surface antigens and marked by 5-bromo-2-deoxyuridine (BrdU). The chitosan porous scaffolds were produced by the method of freeze-drying. The BrdU-labelled BMSCs were co-cultured in vitro with chitosan porous scaffolds, and were observed by scanning electron microscopy. MTT assay was used to observe the cell growth within the scaffold. Fifty adult Sprague Dawley rats were randomly divided into 5 groups with 10 rats in each group. The rat TBI model was made in groups A, B, C, and D according to the principle of Feeney’s free fall combat injury. Orthotopic transplantation was carried out at 72 hours after TBI. Group A was the BMSCs and chitosan porous scaffolds transplantation group; group B was the BMSCs transplantation group; group C was the chitosan porous scaffolds transplantation group; group D was the complete medium transplantation group; and group E was only treated with scalp incision and skull window as sham-operation group. Before TBI and at 1, 7, 14, and 35 days after TBI, the modified neurological severity scores (mNSS) was used to measure the rats’ neurological function. The Morris water maze tests were used after TBI, including the positioning voyage test (the incubation period was detected at 31-35 days after TBI, once a day) and the space exploration test (the number of crossing detection platform was detected at 35 days after TBI). At 36 days after TBI, HE staining and immunohistochemistry double staining [BrdU and neurofilament triplet H (NF-H) immunohistochemistry double staining, and BrdU and glial fibrillary acidic protein (GFAP) immunohistochemistry double staining] were carried out to observe the transplanted BMSCs’ migration and differentiation in the damaged brain areas.ResultsFlow cytometry test showed that the positive rate of CD29 of the 3rd generation BMSCs was 98.49%, and the positive rate of CD45 was only 0.85%. After co-cultured with chitosan porous scaffolds in vitrofor 48 hours, BMSCs were spindle-shaped and secreted extracellular matrix to adhere in the scaffolds. MTT assay testing showed that chitosan porous scaffolds had no adverse effects on the BMSCs’ proliferation. At 35 days after TBI, the mNSS scores and the incubation period of positioning voyage test in group A were lower than those in groups B, C, and D, and the number of crossing detection platform of space exploration test in group A was higher than those in groups B, C, and D, all showing significant differences (P<0.05); but no significant difference was found between groups A and E in above indexes (P>0.05). HE staining showed that the chitosan porous scaffolds had partially degraded, and they integrated with brain tissue well in group A; the degree of repair in groups B, C, and D were worse than that of group A. Immunohistochemical double staining showed that the transplanted BMSCs could survive and differentiate into neurons and glial cells, some differentiated neural cells had relocated at the normal brain tissue; the degree of repair in groups B, C, and D were worse than that of group A.ConclusionThe transplantation of chitosan porous scaffolds combined with BMSCs can improve the neurological deficit of rats following TBI obviously, and also inhabit the glial scar’s formation in the brain damage zone, and can make BMSCs survive, proliferate, and differentiate into nerve cells in the brain damage zone.
Sports-related traumatic brain injury (srTBI) is a traumatic brain injury (TBI) caused by sports, which can result in cognitive and motor dysfunction. Currently, research on the molecular mechanism of srTBI and related drug development mainly relies on monolayer culture models and animal models. However, many differences exist in cell populations and inflammatory responses between these models and human pathophysiological processes. Most of the researches derived from the models can’t effectively conducted translational research. Emerging three-dimensional (3D) in vitro models bridge the limitations of traditional models in simulating the pathophysiological processes of human srTBI and provide new means to understand srTBI. A literature has reported the research progress of emerging 3D in vitro models in neurological diseases, but there is a lack of systematic summary of the mentioned models in srTBI studies. Here, we review the research progress of emerging 3D in vitro models of srTBI, discuss the advantages and limitations of existing models, and further prospect the future trend of srTBI models. This paper aims to provide a new research perspective for researchers in tissue engineering and sports medicine to study the molecular mechanisms of srTBI and develop neuroprotective drugs.
Mild traumatic brain injury has a large number of patients in China. In recent years, studies have pointed out that the return to work is a key goal for rehabilitation, indicating that patients can start integrating into society again and resume normal work and life as soon as possible, which has a positive impact on their rehabilitation. This article summarizes the relevant factors that affect the return to work from four aspects: individual, disease, occupation, and social support, and introduces intervention measures such as follow-up and health education, neuromodulatory technology, symptom management, social support, cognitive and occupational rehabilitation, and multidisciplinary occupational rehabilitation, aiming to provide a reference for promoting the research and development of patients with mild traumatic brain injury returning to work in China.
Correlation between nonlinear subharmonic scattering of ultrasound contrast agent microbubbles and ambient pressure is expected to be used for local brain tissue pressure monitoring. Although high-frequency ultrasound has achieved high-resolution imaging of intracranial microvessels, the research on high-frequency subharmonic scattering characteristics of microbubbles is insufficient at present, which restricts the research progress of estimating local brain tissue pressure based on high-frequency subharmonic scattering of microbubbles. Therefore, under the excitation of 10 MHz high-frequency ultrasound, the effects of different acoustic pressures and ambient pressures on the high-frequency subharmonic scattering characteristics of three different ultrasound contrast agents including SonoVue, Sonazoid and Huashengxian were investigated in this in vitro study. Results showed that the subharmonic scattering amplitudes of the three microbubbles increased with the increase of ambient pressure at the peak negative acoustic pressures of 696, 766 and 817 kPa, and there was a favorable linear correlation between subharmonic amplitude and ambient pressure. Under the above three acoustic pressures, the highest correlation coefficient of SonoVue was 0.948 (P = 0.03), the highest sensitivity of pressure measurement was 0.248 dB/mm Hg and the minimum root mean square error (RMSE) was 2.64 mm Hg. Sonazoid's highest correlation coefficient was 0.982 (P < 0.01), the highest sensitivity of pressure measurement was 0.052 dB/mm Hg and the minimum RMSE was 1.51 mm Hg. The highest correlation coefficient of Huashengxian was 0.969 (P = 0.02), the highest sensitivity of pressure measurement was 0.098 dB/mm Hg and the minimum RMSE was 2.00 mm Hg. The above in vitro experimental results indicate that by selecting ultrasound contrast agent microbubbles and optimizing acoustic pressure, the correlation between high-frequency subharmonic scattering of microbubbles and ambient pressure can be improved, the sensitivity of pressure measurement can be upgraded, and the measurement error can be reduced to meet the clinical demand for local brain tissue pressure measurement, which provided an important experimental basis for subsequent research in vivo.
Objective To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. Methods The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. Results Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. Conclusion TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.