Improvement in cognitive dysfunction following blast induced traumatic brain injury by thymosin α1 in rats: Involvement of inhibition of tau phosphorylation at the Thr205 epitope.

Cognitive impairment is a significant sequela of traumatic brain injury (TBI) especially blast induced traumatic brain injury (bTBI), which is characterized by rapid impairments of learning and memory ability. Although several neuroprotective agents have been postulated as promising drugs for bTBI in animal studies, very few ideal therapeutic options exist to improve cognitive impairment following bTBI. Thymosin α1(Tα1), a 28-amino-acid protein that possesses immunomodulatory functions, has exhibited beneficial effects in the treatment of infectious diseases, immunodeficiency diseases and cancers. However, it remains unclear whether Tα1 has a therapeutic role in bTBI. Thus, we hypothesized that Tα1 administration could reverse the outcomes of bTBI. The blast induced TBI (bTBI) rat model was established with the compressed gas driven blast injury model system. A consecutive Tα1 therapy (in 1 ml saline, twice a day) at a dose of 200 µg/kg or normal saline (NS) (1 ml, twice a day) for 3 days or 2 weeks was performed. Utilizing our newly designed bTBI model, we investigated the beneficial effects of Tα1 therapy on rats exposed to bTBI including: cognitive functions, general histology, regulatory T (Treg) cells, edema, inflammation reactions and the expression and phosphorylation level of tau via Morris Water Maze test (MWM test), HE staining, flow cytometry, brain water content (BWC) calculation, IL-6 assay and Western blotting, respectively. Tα1 treatment seemed to reduce the 24-hour mortality, albeit with no statistical significance. Moreover, Tα1 treatment markedly improved cognitive dysfunction by decreasing the escape latency in the acquisition phase, and increasing the crossing numbers in the probe phase of MWM test. More interestingly, Tα1 significantly inhibited tau phosphorylation at the Thr205 epitope, but not at the Ser404 and Ser262 epitopes. Tα1 increased the percentage of Treg cells and inhibited plasma IL-6 production on 3d post bTBI. Moreover, Tα1 suppressed brain edema as demonstrated by decrease of BWC. However, there was a lack of obvious change in histopathology in the brain upon Tα1 treatment. This is the first study showing that Tα1 improves neurological deficits after bTBI in rats, which is potentially related to the inhibition of tau phosphorylation at the Thr205 epitope, increased Treg cells and decreased inflammatory reactions and brain edema.

A novel model of blast induced traumatic brain injury caused by compressed gas produced sustained cognitive deficits in rats: involvement of phosphorylation of tau at the Thr205 epitope.

Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24 -h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24 -h mortality using peak overpressure fits with the following areas under ROC curves: 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20 cm distance from the blast (about 136.44 kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20 cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12 h, 24 h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12 h after blast injury and significantly increased IL-6 production at 12 h, 24 h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24 h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches.

Neurosurgery medical robot Remebot for the treatment of 17 patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To verify the minimally invasive surgical approach and therapeutic effects of using the medical neurosurgery robot Remebot to treat hypertensive intracerebral hemorrhage (HICH). METHODS: Clinical data for 17 HICH patients were analyzed retrospectively. Hematoma evacuation and tube drainage using Remebot frameless stereotaxic techniques were performed for all patients, and urokinase was injected into the hematomas after the operations. RESULTS: Robot-assisted stereotactic techniques can accurately guide hematoma punctures, and no deaths occurred among these patients. The average positioning error was 1.28 ± 0.49 mm. The average drainage duration was 3.4 days. The 3-month postoperative follow-up revealed improved neurological functions and quality of life for all patients. CONCLUSIONS: The medical neurosurgery robot Remebot is minimally invasive, has high positional accuracy, and facilitates surgical planning according to the shape of the hematoma. Therefore, robot-assisted surgery using Remebot represents a safe and effective treatment method for hematoma evacuation and tube drainage in HICH patients.

Establishment of a novel rat model of blast-related diffuse axonal injury.

Although studies concerning blast-related traumatic brain injury (bTBI) have demonstrated the significance of diffuse axonal injury (DAI), no standard models for this type of injury have been widely accepted. The present study investigated a mechanism of inducing DAI through real blast injury, which was achieved by performing instantaneous high-speed swinging of the rat head, thus establishing a stable animal model of blast DAI. Adult Sprague-Dawley rats weighing 150±10 g were randomly divided into experimental (n=16), control (n=10) and sham control (n=6) groups. The frontal, parietal and occipital cortex of the rats in the experimental group were exposed, whereas those of the control group were unexposed; the sham control group rats were anesthetized and attached to the craniocerebral blast device without experiencing a blast. The rats were subjected to craniocerebral blast injury through a blast equivalent to 400 mg of trinitrotoluene using an electric detonator. Biomechanical parameters, and physical and behavioural changes of the sagittal head swing were measured using a high-speed camera. Magnetic resonance imaging (MRI) scans were conducted at 2, 12, 24 and 48 h after craniocerebral injury, only the experimental group indicated brain stem injury. The rats were sacrificed immediately following the MRI at 48 h for pathological examination of the brain stem using haematoxylin and eosin staining. The results indicated that 14 rats (87.5%) in the experimental group exhibited blast DAI, while no DAI was observed in the control and sham control groups, and the difference between the groups was significant (P<0.05). The present results indicated that this experimental design may serve to provide a stable model of blast DAI in rats.

Surgical management of 142 cases of split cord malformations associated with osseous divide.

OBJECTIVES: To investigate the key surgical points in treating split cord malformations associated with osseous divide and scoliosis (SCM-OD-S). MATERIALS AND METHODS: The surgical options and methods of a total of 142 SCM-OD-S cases were retrospectively analyzed, and the surgical precautions and imaging diagnosis were also discussed. RESULTS: The 142 patients were performed osseous divide resection plus dural sac molding, which achieved good results and no serious complication such as spinal cord and nerve injury occurred; certain symptoms such as urination-defecation disorders, muscle strength subsidence, Pes Cavus, and toe movement disorder in partial patients achieved various degrees of relief, and it also created good conditions for next-step treatment against scoliosis. CONCLUSIONS: The diagnosis of SCM-OD mainly depended on imaging inspection, routine magnetic resonance imaging (MRI) combined with computed tomography (CT) 3D reconstruction, which can comprehensively evaluate the types and features of diastematomyelia as well as other concomitant diseases. SCM alone needed no treatment, but surgery will be the only means of treating SCM-OD. Intraoperatively removing osseous divide step-by-step, as well as carefully freeing the spinal cord and remodeling the dural sac, can lay good foundations for relieving tethered cord, improving neurological symptoms, and further scoliosis orthomorphia, thus particularly exhibiting importance for the growth and development of adolescents.

Analysis of floral transcription factors from Lycoris longituba.

Transcription factors (TFs) are proteins that bind to specific promoter regions of their target genes and regulate gene transcription. Many of these factors have been found to influence flowering. Lycoris longituba exhibits a great deal of diversity in flower color and flower form, making it a suitable model for the study of floral development. We have identified 338 putative TFs from more than thirty thousand ESTs sequenced from the floral tissue of L. longituba, and validated them using real-time RT-PCR. Fifty-one of the TFs were recognized as being potentially flower-specific, and the expression patterns of some of them during six flowering phases have been elucidated. Homolog annotation and phylogenetic analysis revealed that some TFs that belong to several TF families, such as MADS, MYB-related, NAC, and ABI3-VP1, were suggested to play important roles in the flowering process. Our dataset may be used to identify priority target TF genes for further study.

[Characteristic of medical support and health care for Shenzhou-5 and Shenzhou-6 astronauts at main landing site].

OBJECTIVE: To investigate the characteristics of medical support and health care for the Shenzhou-5 and Shenzhou-6 astronauts at the main landing site, with special emphasis on the technical requirements for two astronauts during flight, in order to provide reference data for medical support in the battle field and disasters. METHODS: The data associated with accidental injuries of astronauts during the space flight collected from foreign nations and domestically were reviewed retrospectively. Based on the experience in medical support for Shenzhou-5 and Shenzhou-6 astronauts and the special environments of field operations, a scheme for first-aid and emergent treatment were drafted for a system of organization, prophylactic measurements, equipment and their effective implementation pending the test in the real situation. RESULTS: Two sets of high-quality intensive care unit (ICU) equipment were set up in helicopters, and an ambulance was equipped with the instruments and facilities that could be used in the first-aid and surgical operation in case accident and injuries should happen. The three sets of highly mobile ICU mentioned above could cover a vast area of both grassland and desert at the landing site to ensure that the astronauts could be rescued should accident occur, reaction to emergency would be most rapid and technique and equipment would be best. This scheme of first-aid for emergency which might occur in astronauts would seem to be a scientific, reasonable and practical system and would also meet the need in battle field. CONCLUSION: The first-aid scheme for astronauts at the main landing site, and its equipment, first aid strategies as well as it execution might provide an advanced system for medical aid and emergency treatment in the battlefield, disasters, and other special occasions.

[Establishment of a mobile intensive care unit].

OBJECTIVE: To discuss the experience of establishment of a mobile intensive care unit (ICU) for emergency treatment following astronaut flight, disaster, and regional war. METHODS: The data from both foreign and our countries as well as our own clinical experience of first-aid were reviewed, and a mobile ICU was established, including the equipment, supply of drugs, training, and organization. RESULTS: The mobile ICU was set up at the site of landing of the first Chinese astronaut, and proved to be efficient. The new model could be expected to be prompt in first-aid for casualties in disasters and warfare. CONCLUSION: The first-aid on spot of casualties might reduce the rates of invalidity and mortality during disasters and regional war.

[Measure on medical care and rescue for the first Chinese astronaut during manned space flight].

OBJECTIVE: To discuss the experience of medical care and rescue for the first Chinese astronaut during manned space flight. METHODS: Review the experiences of foreign nations in respect to accidental injuries of astronaut during manned space flight, the possible reasons were analyzed, and accordingly a reasonable and effective prophylactic measures and health care were formulated. RESULTS: An effective mobile intensive care unit (ICU) was established on desert or prairie where the capsule would land, so as to ensure the safety of the first Chinese astronaut, and to provide intensive care as well as successful emergency treatment in case of accidental injuries. CONCLUSION: Reasonable and effective prophylactic measures and health care appear to be an important aspect of the successful manned space flight.