Application of artificial hibernation technology in acute brain injury.

Controlling intracranial pressure, nerve cell regeneration, and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury. There is currently a lack of effective treatment methods. Hibernation has the characteristics of low temperature, low metabolism, and hibernation rhythm, as well as protective effects on the nervous, cardiovascular, and motor systems. Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body's metabolism, lowering the body's core temperature, and allowing the body to enter a state similar to hibernation. This review introduces artificial hibernation technology, including mild hypothermia treatment technology, central nervous system regulation technology, and artificial hibernation-inducer technology. Upon summarizing the relevant research on artificial hibernation technology in acute brain injury, the research results show that artificial hibernation technology has neuroprotective, anti-inflammatory, and oxidative stress-resistance effects, indicating that it has therapeutic significance in acute brain injury. Furthermore, artificial hibernation technology can alleviate the damage of ischemic stroke, traumatic brain injury, cerebral hemorrhage, cerebral infarction, and other diseases, providing new strategies for treating acute brain injury. However, artificial hibernation technology is currently in its infancy and has some complications, such as electrolyte imbalance and coagulation disorders, which limit its use. Further research is needed for its clinical application.

Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage: phase I clinical trial.

Animal experiments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury. To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage, this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion criteria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People's Armed Police Force from May 2016 to December 2020. Patients were divided into three groups according to the clinical situation and patient benefit: control (n = 18), human umbilical cord-derived mesenchymal stem cells (n = 4), and combination (n = 8). The control group did not receive any transplantation. The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation. The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells. Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intracerebral hemorrhage-related encephalomalacia. Severe adverse events associated with cell transplantation were not observed. Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Glycolysis-related lncRNA TMEM105 upregulates LDHA to facilitate breast cancer liver metastasis via sponging miR-1208.

Increased glycolysis is one of the key metabolic hallmarks of cancer cells. However, the roles of lncRNAs in energy metabolism and cancer metastasis remain unclear. Here, the expression of TMEM105 associated with glycolysis was dramatically elevated from normal to breast cancer to breast cancer liver metastasis tissues, and the survival analysis revealed that high TMEM105 expression was related to poor survival, especially in patients with liver metastasis. Moreover, TMEM105 facilitated the glycolysis of breast cancer cells and induced cell invasion and breast cancer liver metastasis (BCLM). Mechanistically, TMEM105 regulated LDHA expression by sponging miR-1208, which further promoted cell glycolysis and BCLM. Importantly, glycolytic production of lactate enhanced TMEM105 expression in breast cancer cells by activating the SHH-MAZ signaling pathway. These findings suggested that the lactate-responsive TMEM105 acted as a miRNA sponge, inducing BCLM via a glycolysis-mediated positive feedback loop, which might be a rational target for the treatment of BCLM patients.

Study on mass transfer in the bone lacunar-canalicular system under different gravity fields.

INTRODUCTION: The bone lacunar-canalicular system (LCS) is an important microstructural basis for signaling and material transport in bone tissue, guaranteeing normal physiological processes in tissues. Spaceflight astronauts and elderly osteoporosis are related to its function, so it is necessary to reveal the mass transfer laws in bone microstructure under different gravity fields to provide insight for effective clinical treatment. MATERIALS AND METHODS: Using the natural LCS structure of bovine tibial cortical bone as the object, the mass transfer experiments on cortical bone were conducted by using sodium fluorescein tracer through different frequency pulsating pressure provided by dynamic perfusion loading device and different high G environments provided by high-speed centrifuge to analyze the mass transfer laws under different gravity fields and different pulsating pressures. RESULTS: The fluorescence intensity of lacunae within the osteon was lower the farther away from the Haversian canal. As the gravity field magnitude increased, the fluorescence intensity within each lacuna enhanced, and the more distant the lacunae from the Haversian canal, the greater the fluorescence intensity enhancement. High-frequency pulsating pressure simulated high-intensity exercise in humans can improve mass transfer efficiency in the LCS. CONCLUSION: High-intensity exercise may greatly increase solute molecules, nutrients, and signaling molecules in osteocytes and improve the activity of osteocytes. Hypergravity can enhance the transport of solute molecules, nutrients, and signaling molecules in the LCS, especially promoting mass transfer to deep layer lacunae. Conversely, mass transfer to deep layer lacunae may be inhibited under microgravity, causing bone loss and ultimately leading to osteoporosis.

Three-dimensional-printed collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural network reconstruction in canines with traumatic brain injury.

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury (TBI). We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds (3D-CC-ST) on the injured tissue regeneration process. 3D-CC-ST was performed using 3D printing technology at a low temperature (-20°C), and the physical properties and degeneration rate were measured. The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells. Immediately after the establishment of the canine TBI model, 3D-CC-ST and 3D-CC (3D-printed collagen/chitosan scaffolds) were implanted into the cavity of TBI. Following implantation of scaffolds, neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery. Histological and immunofluorescence staining were performed to evaluate neuro-regeneration. The group treated with 3D-CC-ST had good performance of behavior functions. Implanting 3D-CC-ST significantly reduced the cavity area, facilitated the regeneration of nerve fibers and vessel reconstruction, and promoted endogenous neuronal differentiation and synapse formation after TBI. The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.

Sustained developmental endothelial locus-1 overexpression promotes spinal cord injury recovery in mice through the SIRT1/SERCA2 signaling pathway.

Although the anti-inflammatory properties of developmental endothelial locus-1 (DEL-1) are well known, few studies have examined the role of DEL-1 in spinal cord injury (SCI). Here, the protective effect of DEL-1 on SCI was investigated using hypoxia/recovery (H/R) injury of astrocytes and a mouse SCI model. The effects of DEL-1 overexpression/silencing on primary astrocytes were assessed by flow cytometry, immunofluorescence, and western blotting. Female Sprague-Dawley rats were intrathecally injected with recombinant adeno-associated virus (AAV) at T10, and DEL-1 was permanently expressed. Protein levels in the spinal cord, functional testing, and electrophysiology, pathology, and immunofluorescence were all measured after treatment. DEL-1 overexpression significantly increased the expression of SIRT1/SERCA2At the same time, inflammation, endoplasmic reticulum stress, and apoptosis were all significantly inhibited, the motor function of SCI rats was noticeably restored, and the myelin sheath of the injured site was more complete. Furthermore, after DEL-1 silencing SIRT1/SERCA2 expression decreased, while inflammation, endoplasmic reticulum stress, and apoptotic responses increased significantly. DEL-1 treatment, however, did not increase SERCA2 expression after SIRT1 silencing. These findings demonstrate that DEL-1 protects against SCI via SIRT1/SERCA2 signaling, promoting spinal neural recovery.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells.

OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

SUMMARY OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

A Study of the Brain Network Connectivity in Visual-Word Pairing Associative Learning and Episodic Memory Reactivating Task.

Episodic memory allows a person to recall and mentally reexperience specific episodes from one's personal past. Studies of episodic memory are of great significance for the diagnosis and the exploration of the mechanism of memory generation. Most of the current studies focus on certain brain regions and pay less attention to the interrelationship between multiple brain regions. To explore the interrelationship in the brain network, we use an open fMRI dataset to construct the brain functional connectivity and effective connectivity network. We establish a binary directed network of the memory when it is reactivated. The binary directed network shows that the occipital lobe and parietal lobe have the most causal connections. The number of edges starting from the superior parietal lobule is the highest, with 49 edges, and 31 of which are connected to the occipital cortex. This means that the interaction between the superior parietal lobule and the occipital lobe plays the most important role in episodic memory, and the superior parietal lobule plays a more causal role in causality. In addition, memory regions such as the precuneus and fusiform also have some edges. The results show that the posterior parietal cortex plays an important role of hub node in the episodic memory network. From the brain network model, more information can be obtained, which is conducive to exploring the brain's changing pattern in the whole memory process.

Collagen/heparin sulfate scaffold combined with mesenchymal stem cells treatment for canines with spinal cord injury: A pilot feasibility study.

BACKGROUND: Due to endogenous neuronal deficiency and glial scar formation, spinal cord injury (SCI) often leads to irreversible neurological loss. Accumulating evidence has shown that a suitable scaffold has important value for promoting nerve regeneration after SCI. Collagen/heparin sulfate scaffold (CHSS) has shown effect for guiding axonal regeneration and decreasing glial scar deposition after SCI. The current research aimed to evaluate the utility of the CHSSs adsorbed with mesenchymal stem cells (MSCs) on nerve regeneration, and functional recovery after acute complete SCI. METHODS: CHSSs were prepared, and evaluated for biocompatibility. The CHSSs adsorbed with MSCs were transplanted into these canines with complete SCI. RESULTS: We observed that MSCs had good biocompatibility with CHSSs. In complete transverse SCI models, the implantation of CHSS co-cultured with MSCs exhibited significant improvement in locomotion, motor evoked potential, magnetic resonance imaging, diffusion tensor imaging, and urodynamic parameters. Meanwhile, nerve fibers were markedly improved in the CHSS adsorbed with MSCs group. Moreover, we observed that the implantation of CHSS combined with MSCs modulated inflammatory cytokine levels. CONCLUSIONS: The results preliminarily demonstrated that the transplantation of MSCs on a CHSS could improve the recovery of motor function after SCI. Thus, implanting the MSCs-laden CHSS is a promising combinatorial therapy for treatment in acute SCI.

PCAT-1 facilitates breast cancer progression via binding to RACK1 and enhancing oxygen-independent stability of HIF-1α.

Hypoxia induces a series of cellular adaptive responses that enable promotion of inflammation and cancer development. Hypoxia-inducible factor-1α (HIF-1α) is involved in the hypoxia response and cancer promotion, and it accumulates in hypoxia and is degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxia-inducible long non-coding RNA (lncRNA) that regulates HIF-1α stability, crucial for cancer progression. Extensive analyses of clinical data indicate that PCAT-1 is elevated in breast cancer patients and is associated with pathological grade, tumor size, and poor clinical outcomes. Through gain- and loss-of-function experiments, we find that PCAT-1 promotes hypoxia-associated breast cancer progression including growth, migration, invasion, colony formation, and metabolic regulation. Mechanistically, PCAT-1 directly interacts with the receptor of activated protein C kinase-1 (RACK1) protein and prevents RACK1 from binding to HIF-1α, thus protecting HIF-1α from RACK1-induced oxygen-independent degradation. These findings provide new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest a novel role of PCAT-1 as a potential therapeutic target for breast cancer.

The corticospinal tract structure of collagen/silk fibroin scaffold implants using 3D printing promotes functional recovery after complete spinal cord transection in rats.

No effective treatment has been established for nerve dysfunction caused by spinal cord injury (SCI). Orderly axonal growth at the site of spinal cord transection and creation of an appropriate biological microenvironment are important for functional recovery. To axially guiding axonal growth, designing a collagen/silk fibroin scaffold fabricated with 3D printing technology (3D-C/SF) emulated the corticospinal tract. The normal collagen/silk fibroin scaffold with freeze-drying technology (C/SF) or 3D-C/SF scaffold were implanted into rats with completely transected SCI to evaluate its effect on nerve repair during an 8-week observation period. Electrophysiological analysis and locomotor performance showed that the 3D-C/SF implants contributed to significant improvements in the neurogolical function of rats compared to C/SF group. By magnetic resonance imaging, 3D-C/SF implants promoted a striking degree of axonal regeneration and connection between the proximal and distal SCI sites. Compared with C/SF group, rats with 3D-C/SF scaffold exhibited fewer lesions and disordered structures in histological analysis and more GAP43-positive profiles at the lesion site. The above results indicated that the corticospinal tract structure of 3D printing collagen/silk fibroin scaffold improved axonal regeneration and promoted orderly connections within the neural network, which could provided a promising and innovative approach for tissue repair after SCI.

Implantation of regenerative complexes in traumatic brain injury canine models enhances the reconstruction of neural networks and motor function recovery.

Rationale: The combination of medical and tissue engineering in neural regeneration studies is a promising field. Collagen, silk fibroin and seed cells are suitable options and have been widely used in the repair of spinal cord injury. In this study, we aimed to determine whether the implantation of a complex fabricated with collagen/silk fibroin (SF) and the human umbilical cord mesenchymal stem cells (hUCMSCs) can promote cerebral cortex repair and motor functional recovery in a canine model of traumatic brain injury (TBI). Methods: A porous scaffold was fabricated with cross-linked collagen and SF. Its physical properties and degeneration rate were measured. The scaffolds were co-cultured with hUCMSCs after which an implantable complex was formed. After complex implantation to a canine model of TBI, the motor evoked potential (MEP) and magnetic resonance imaging (MRI) were used to evaluate the integrity of the cerebral cortex. The neurologic score, motion capture, surface electromyography (sEMG), and vertical ground reaction force (vGRF) were measured in the analysis of motor functions. In vitro analysis of inflammation levels was performed by Elisa while immunohistochemistry was used in track the fate of hUCMSCs. In situ hybridization, transmission electron microscope, and immunofluorescence were used to assess neural and vascular regeneration. Results: Favorable physical properties, suitable degradation rate, and biocompatibility were observed in the collagen/SF scaffolds. The group with complex implantation exhibited the best cerebral cortex integrity and motor functions. The implantation also led to the regeneration of more blood vessels and nerve fibers, less glial fibers, and inflammatory factors. Conclusion: Implantation of this complex enhanced therapy in traumatic brain injury (TBI) through structural repair and functional recovery. These effects exhibit the translational prospects for the clinical application of this complex.

Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway.

OBJECTIVE: To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. METHODS: Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. RESULTS: Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05). CONCLUSIONS: Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury.

One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site, resulting in poor adhesion and proliferation of neural stem cells at the injured area. To enhance the targeted delivery of exogenous stem cells to the injury site, cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury. Collagen/heparan sulfate porous scaffolds, prepared using a freeze-drying method, have stable physical and chemical properties. These scaffolds also have good cell biocompatibility because of their high porosity, which is suitable for the proliferation and migration of neural stem cells. In the present study, collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury, which was established using the controlled cortical impact method. At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells, there was significantly improved regeneration of neurons, nerve fibers, synapses, and myelin sheaths in the injured brain tissue. Furthermore, brain edema and cell apoptosis were significantly reduced, and rat motor and cognitive functions were markedly recovered. These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury. This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People's Armed Police Force, China (approval No. 2017-0007.2) on February 10, 2019.

Collagen/heparin scaffold combined with vascular endothelial growth factor promotes the repair of neurological function in rats with traumatic brain injury.

The objective of this study was to evaluate the therapy effects of a novel biological scaffold containing heparin, collagen and vascular endothelial growth factor (VEGF) in treating traumatic brain injury (TBI). In our research, a functional composite scaffold constituted by collagen, heparin and vascular endothelial growth factor was used to stimulate angiogenesis and improve nerve-tissue regeneration in a rat model of TBI. The composite scaffold possessed excellent mechanical properties and good porosity, and could effectively control the release rate of VEGF. Motor and cognitive functions such as motor evoked potential, Morris water maze test and modified neurological severity score were evidently improved after the scaffold was grafted onto the injury site in the rat TBI model. There was clearly improved restoration of damaged nerve tissue at the injured site. Furthermore, brain edema and inflammatory reactions were significantly alleviated. Newly formed neurons with associated synaptic structures, nerve fibers, myelin sheaths and functional angiogenesis with intact endothelium at the injury site were observed. In conclusion, our data revealed that the collagen/heparin scaffold combined with VEGF could create excellent microenvironment stimuli for damaged nerve-tissue regeneration, providing a potential strategy for treating TBI.

Markerless Rat Behavior Quantification With Cascade Neural Network.

Quantifying rat behavior through video surveillance is crucial for medicine, neuroscience, and other fields. In this paper, we focus on the challenging problem of estimating landmark points, such as the rat's eyes and joints, only with image processing and quantify the motion behavior of the rat. Firstly, we placed the rat on a special running machine and used a high frame rate camera to capture its motion. Secondly, we designed the cascade convolution network (CCN) and cascade hourglass network (CHN), which are two structures to extract features of the images. Three coordinate calculation methods-fully connected regression (FCR), heatmap maximum position (HMP), and heatmap integral regression (HIR)-were used to locate the coordinates of the landmark points. Thirdly, through a strict normalized evaluation criterion, we analyzed the accuracy of the different structures and coordinate calculation methods for rat landmark point estimation in various feature map sizes. The results demonstrated that the CCN structure with the HIR method achieved the highest estimation accuracy of 75%, which is sufficient to accurately track and quantify rat joint motion.

3D printing collagen/heparin sulfate scaffolds boost neural network reconstruction and motor function recovery after traumatic brain injury in canine.

Tissue engineering is considered highly promising for the repair of traumatic brain injury (TBI), and accumulating evidence has proved the efficacy of biomaterials and 3D printing. Although collagen is famous for its natural properties, some defects still restrict its potential applications in tissue repair. In this experimental study, we fabricated a kind of scaffold with collagen and heparin sulfate via 3D printing, which possesses favorable physical properties and suitable degradation rate along with satisfactory cytocompatibility. After implantation, the results of motor evoked potentials (MEPs) showed that the latency and amplitude can both be improved in hemiplegic limbs, and the structural integrity of the cerebral cortex and corticospinal tract can be enhanced significantly under magnetic resonance imaging (MRI) evaluation. Additionally, the results of in situ hybridization (ISH) and immunofluorescence staining also revealed the facilitating role of 3D printing collagen/heparin sulfate scaffolds on vascular and neural regeneration. Moreover, the individuals implanted with this kind of scaffold present better gait characteristics and preferable electromyography and myodynamia. In general, 3D printed collagen/heparin sulfate scaffolds have superb performance in both structural repair and functional improvement and may offer a new strategy for the repair of TBI.