Evidence that robot-assisted gait training modulates neuroplasticity after stroke: An fMRI pilot study based on graph theory analysis.

OBJECTIVES: To investigate alterations of whole-brain network after stroke and therapeutic mechanisms of robot-assisted gait training (RAGT). METHODS: 21 stroke patients and 20 healthy subjects were enrolled, with the stroke patients randomized to either control group (n = 11) or robot group (n = 10), and resting-state functional magnetic resonance imaging data were collected. The global network metrics were obtained using graph theory analysis and compared between stroke patients and healthy subjects, and the effect of the RAGT on the whole-brain networks was explored. RESULTS: Compared to healthy subjects, area under the curve (AUC) for small-worldness (σ), clustering coefficient (Cp), global efficiency (Eg) and mean local efficiency (Eloc) were significantly lower in stroke patients, whereas AUC for characteristic path length (Lp) were significantly higher. Compared with the control group, patients in robot group showed significant improvement in lower limb motor function, balance function and walking function after intervention, with a significant reduction in the AUC of Cp. Moreover, the improvement of walking function was positively correlated with the changes of AUC of σ and Eg, and negatively correlated with the changes of AUC of Cp. CONCLUSIONS: Small-worldness and network efficiency were significantly reduced after stroke, whereas RAGT decreased characteristic path length and promoted normalization of the whole-brain network, and this change was associated with improvement in walking function. Our findings reveal the mechanism by which RAGT regulates network reorganization and neuroplasticity after stroke.

Corrigendum: Functional networks in prolonged disorders of consciousness.

[This corrects the article DOI: 10.3389/fnins.2023.1113695.].

Functional networks in prolonged disorders of consciousness.

Prolonged disorders of consciousness (DoC) are characterized by extended disruptions of brain activities that sustain wakefulness and awareness and are caused by various etiologies. During the past decades, neuroimaging has been a practical method of investigation in basic and clinical research to identify how brain properties interact in different levels of consciousness. Resting-state functional connectivity within and between canonical cortical networks correlates with consciousness by a calculation of the associated temporal blood oxygen level-dependent (BOLD) signal process during functional MRI (fMRI) and reveals the brain function of patients with prolonged DoC. There are certain brain networks including the default mode, dorsal attention, executive control, salience, auditory, visual, and sensorimotor networks that have been reported to be altered in low-level states of consciousness under either pathological or physiological states. Analysis of brain network connections based on functional imaging contributes to more accurate judgments of consciousness level and prognosis at the brain level. In this review, neurobehavioral evaluation of prolonged DoC and the functional connectivity within brain networks based on resting-state fMRI were reviewed to provide reference values for clinical diagnosis and prognostic evaluation.

Theaflavic acid from black tea protects PC12 cells against ROS-mediated mitochondrial apoptosis induced by OGD/R via activating Nrf2/ARE signaling pathway.

Cerebral ischemic stroke is a severe disease afflicting people worldwide. Phytochemicals play a pivotal role in the discovery of novel therapeutic approaches for the prevention of ischemic stroke. In our continual search for bioactive natural products for the treatment of ischemic stroke, we have evaluated the protective effects of theaflavic acid (TFA) from black tea using PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R), and investigated the possible mechanisms. The results showed that TFA can protect PC12 cells against OGD/R through increasing cell viability and decreasing intracellular lactate dehydrogenase (LDH) release. Further investigations found that TFA could inhibit the overproduction of intracellular reactive oxygen species (ROS), reduce malondialdehyde content, and elevate superoxide dismutase activity, which implied that TFA suppresses oxidative stress in PC12 cells induced by OGD/R. In addition, overload of intracellular calcium and collapse of the mitochondrial membrane potential were improved in the presence of TFA, and the activity of caspase-3 was significantly reduced by TFA. Western blot analysis showed that the expression of Bcl-2 was up-regulated while Bax was down-regulated. Therefore, it can be concluded that TFA can inhibit mitochondria-dependent apoptosis of PC12 cells induced by OGD/R. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway was explored to elucidate the mechanism by which TFA inhibits ROS-mediated apoptosis in PC12 cells. The results revealed that TFA promoted the translocation of Nrf2 into nuclei, enhanced the transcriptional activity of ARE, and up-regulated expression of downstream HO-1, which indicates that the Nrf2/ARE signaling pathway is involved in the protection by TFA of PC12 cells injured by OGD/R.

Differences in Cognitive Function of Rats with Traumatic Brain Injuries Following Hyperbaric Oxygen Therapy.

BACKGROUND Hyperbaric oxygen (HBO) is a historical therapeutic option in the treatment of various types of brain damage. At present, clinical treatment of hypoxic-ischemic injury is giving priority to cognitive training. The effects of HBO on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model. MATERIAL AND METHODS Seventy male SD rats were randomly divided into control (n=10) and intervention (n=60) groups. All rats underwent baseline water maze testing 1 day before modeling, and were retested 8 weeks after modeling. The percentage of residence time during escape latency in the target quadrant and the total time were recorded. Data were analyzed by SPSS 16.0 software. P<0.05 was considered statistically significant. RESULTS After 8 weeks, no statistical difference (P>0.05) existed in spatial learning ability in the 3-day and 5-day groups when compared with baseline. The other groups were statistically different by auto-comparison (P<0.05). No statistical difference (P>0.05) in spatial memory existed in the 5-day and 1-week groups when compared with baseline, while a significant difference was noted in the other groups by self-comparison (P<0.05). No statistical difference (P>0.05) was noted in the level of expression of growth-associated protein-43 (GAP-43) and synaptophysin (Syn) in the 1-day group compared with the control group. The remaining groups and the control group were statistically different (P<0.05), while the level of expression of GAP-43 and Syn in the 5-day, 1-week, and 2-week groups was significantly different compared with that in the control group (P<0.01). CONCLUSIONS If HBO therapy was provided 5-7 days after craniocerebral trauma, there was apparent improvement in cognitive function and neuroplasticity.

Music-supported therapy (MST) in improving post-stroke patients' upper-limb motor function: a randomised controlled pilot study.

OBJECTIVE: Music-supported therapy (MST) is a new approach for motor rehabilitation of stroke patients. Recently, many studies have demonstrated that MST improved the motor functions of post-stroke patients. However, the underlying mechanism for this effect is still unclear. It may result from repeated practice or repeated practice combined with musical stimulation. Currently, few studies have been designed to clarify this discrepancy. In this study, the application of "mute" musical instruments allowed for the study of music as an independent factor. METHODS: Thirty-three post-stroke patients with no substantial previous musical training were included. Participants were assigned to either audible music group (MG) or mute music group (CG), permitting observation of music's independent effect. All subjects received the conventional rehabilitation treatments. Patients in MG (n = 15) received 20 extra sessions of audible musical instrument training over 4 weeks. Patients in CG (n = 18) received "mute" musical instrument training of the same protocol as that of MG. Wolf motor function test (WMFT) and Fugl-Meyer assessment (FMA) for upper limbs were utilised to evaluate motor functions of patients in both groups before and after the treatment. Three patients in CG dropped out. RESULTS: All participants in both groups showed significant improvements in motor functions of upper limbs after 4  weeks' treatment. However, significant differences in the WMFT were found between the two groups (WMFT-quality: P = 0.025; WMFT-time: P = 0.037), but not in the FMA (P = 0.448). In short, all participants showed significant improvement after 4 weeks' treatment, but subjects in MG demonstrated greater improvement than those in CG. DISCUSSION: This study supports that MST, when combined with conventional treatment, is effective for the recovery of motor skills in post-stroke patients. Additionally, it suggests that apart from the repetitive practices of MST, music may play a unique role in improving upper-limb motor function for post-stroke patients.

Assessing consciousness with auditory event-related potential during coma recovery: a case study.

To observe changes in mismatch negativity (MMN) and P300 in a patient transitioning from a vegetative state (VS) to a minimally conscious state (MCS). One patient with intracerebral hemorrhage and an 8-month disease course was evaluated as being in the VS using the Coma Recovery Scale-Revised. Two weeks after the patient was admitted to the hospital, another evaluation was performed, and the patient was determined to be in an MCS. Using the Oddball paradigm, pure tone and name stimuli were presented to the patient to study event-related potentials (ERPs). A 15-week clinical follow-up was carried out, and four ERP examinations were performed at 2 days and 2, 6, and 15 weeks after admission. One healthy individual was assessed as a control participant. MMN and P300 were elicited in all four ERP examinations. MMN and P300 may occur earlier than believed in patients in persistent VS and MCS; their predictive values for prognosis need to be further confirmed by follow-up studies on a large clinical sample.

The effect and mechanism of growth hormone replacement on cognitive function in rats with traumatic brain injury.

OBJECTIVE: The effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model and the underlying mechanism was explored. METHOD: Three-month-old male SD rats were randomly divided into sham (n = 10), control (n = 10), and CCI groups (n = 40) The parameters were set as follows: striking speed, 3.5 m/s; impact depth, 1.5 mm; and dwell time, 400 msec. Eight and ten weeks post-injury, the GH levels were measured the water maze test and novel object recognition test were performed. CCI rats were divided into normal and decreased GH groups, and further randomly divided into two sub-groups (rhGH treatment and saline vehicle groups). All rats were tested for SYN, BDNF, and TrkB mRNA in the prefrontal cortex and hippocampus by RT-PCR. RESULTS: CCI rats 8 weeks post-injury had cognitive dysfunction regardless of the GH level (P<0.05). rhGH treatment improved cognitive function in CCI rats. There was a positive correlation between the expression of prefrontal BDNF and SYN mRNA in CCI rats after rhGH therapy and the water maze test score (r = 0.773 and 0.534, respectively; P<0.05). Furthermore, the expression of BDNF, TrkB, and SYN mRNA in the hippocampus was negatively correlated with the water maze test score (r = 0.602, 0.773, 0.672, and 0.783, respectively; P<0.05). There was a difference in the expression of hippocampal and prefrontal BDNF, TrkB, and SYN mRNA (P<0.05). CONCLUSION: rhGH treatment had a positive effect on cognitive function, which was more evident in GH-deficient rats. The increased expression of hippocampal and prefrontal BDNF and TrkB mRNA is implicated in rhGH therapy to improve cognitive function. Changes in the expression of hippocampal SYN mRNA following rhGH therapy may also play a role in improving cognitive function.

Three cases of acute gastroenteritis caused by high-level macrolideresistant Campylobacter: drug resistance mechanisms and clinical characteristics.

We report 3 cases of acute gastroenteritis caused by high-level macrolide-resistant Campylobacter. The clinical characteristics of patients were studied, and the rplD, rplV, and 23S rRNA domain V genes were sequenced to detected resistance-related mutations.

Clinical manifestations of Campylobacter jejuni infection in adolescents and adults, and change in antibiotic resistance of the pathogen over the past 16 years.

BACKGROUND: Campylobacter jejuni infection, traditionally a paediatric illness, is now seen more frequently in adolescents and adults in northern China. Published surveillance reports on C. jejuni infection in these patients are rare. We aimed to characterize (1) the clinical manifestations of this infection in adolescents and adults, and (2) changes in antibiotic resistance of the pathogen. METHODS: We retrospectively examined 492 cases of C. jejuni infection in patients aged ≥ 14 y treated at the Peking University First Hospital, Beijing, China, for the period January 1994 to December 2010. RESULTS: The disease was more common in patients aged 14-24 y and in men (57.9%; p < 0.0001 vs women). The peak incidence was seen between May and October. The infection manifested with acute diarrhoea (< 10 bowel movements per day, loose or mucous stool), fever (mostly low grade), and abdominal cramps and pain. Faecal leukocytes and erythrocytes were demonstrated in, respectively, 90.9% and 79.3% of stool specimens, while leukocytes > 10 per high-power field were detected in 70.3%. In 1994-1998, 44.5% of C. jejuni strains were resistant to fluoroquinolone, 0% to gentamicin, and 0% to cefuroxime; in 2005-2010, resistance increased significantly to 97.9%, 16.7%, and 93.0%, respectively (p < 0.0001). The resistance to erythromycin did not change significantly (3% vs 6.4%, p = 0.4). CONCLUSIONS: Manifestations of C. jejuni infection in adolescent and adult patients are similar to those in children. Over the 16-y study period, resistance of C. jejuni to fluoroquinolones, gentamicin, and cefuroxime significantly increased.

Campylobacter enteritis in adult patients with acute diarrhea from 2005 to 2009 in Beijing, China.

BACKGROUND: There has been a marked global increase in the incidence of human Campylobacter enteritis in recent years. This study investigated the epidemiological and clinical features of Campylobacter enteritis in adult patients suffering from acute diarrhea. METHODS: This was a retrospective review of Campylobacter enteritis in adult patients with acute diarrhea presenting at Beijing University First Hospital, Beijing, China, in the summer and autumn (April to October) of 2005 to 2009. The data collected included the species of campylobacter identified, and the age, gender, clinical manifestations and results of laboratory test on stool samples collected from the patients. Campylobacter sensitivity tests to various antimicrobial agents were conducted on 80 specimens. Chi-square tests were applied using SPSS13.0 software and a two-sided P value of < 0.05 was considered statistically significant. RESULTS: Campylobacter spp. isolated from the stool specimens of 142 patients with diarrhea represented 14.9% of all the cases examined. C. jejuni was identified in 127 patients (89.4%) and C. coli in 15 others (10.6%). The infection incidence was highest in the age range of 21 - 30 years which comprised 21.7% of the total cases examined. Most cases of diarrhea (46 patients) occurred in June. Watery diarrhea (97.2%), abdominal pain (72.5%) and fever (64.8%) were the most common manifestations of enteric campylobacteriosis. Only four patients (2.8%) had bloody diarrhea. The antimicrobial resistance rates were: cefoperazone (100%), levofloxacin (61.3%), gentamicin (12.5%), erythromycin (6.3%), and azithromycin (2.5%). CONCLUSIONS: Campylobacter was prevalent among adults with acute diarrhea from 2005 to 2009 in Beijing, China. The large number of those afflicted by the disease warrants the commission of a large multicenter study to determine the extent of enteric campylobacteriosis in this region.

[Effects of needle retaining at Zusanli (ST 36) on hemodynamic change of anterior tibial artery].

OBJECTIVE: To observe the effects of needle retaining on hemodynamic change and investigate the significance of retaining needle. METHODS: Manual acupuncture was performed at the left Zusanli (ST 36) of 26 healthy adult volunteers who have not receiued acupuncture. 26 cases were randomly divided into a needle retaining group and a quick needling group, 13 cases in each group. Hemodynamic parameters of the anterior tibial artery were observed with color Doppler ultrasound before needling and 0, 1, 2, 3, 4 and 5 minutes after needle manipulation. Hemodynamic parameters were also compared between the two groups 0, 1, 2, 3, 4 and 5 minutes after needle manipulation. RESULTS: There were no significant difference in V(max) and Vm between 0, 1, 2, 3, 4 and 5 minutes after needling manipulation (all P > 0.05). CONCLUSION: Needle retaining can not change regional hemodynamic.

[Construction of HLA-A2-peptide tetramer and application in HBV/HCV infection].

OBJECTIVE: To construct HBV and HCV-specific HLA-A2-peptide tetramers, and to direct clinical therapy. METHODS: Recombinant class I HLA-A2 heavy chains and beta-2 M were produced in Escherichia coli cells transformed with pBV220 vectors. Only the extracellular domain of class I heavy chain was expressed, following modification by replacement of the C-terminal domain with a substrate sequence for BirA biotinylation. HLA-A2-BSP was folded in the presence of beta-2 microglobulin and a specific peptide to form a peptide-MHC complex. The MHC complexes were biotinylated using purified BirA enzyme. Biotinylated MHC-peptide complexes were purified. Tetramers were generated by mixing biotinylated protein complex with streptavidin-PE at a molar ratio of 4:1. Then analysis of stained PBMCs was performed using FACScan and CellQuest software. RESULTS: The expression levels of pBV220-HLA-A2-BSP and beta-2M were 46% and 48% of total bacterial proteins estimated from SDS - PAGE, respectively. And they were mainly located in the insoluble fraction of the cell as inclusion bodies and the proportion were about 85% and 90%, respectively. The purity of pBV220-HLA-A2-BSP and beta-2M was above 95% analyzed by SDS-PAGE, and the concentration of pBV220-HLA-A2-BSP and beta-2M was about 1.5 g/L and 1.2 g/L, respectively. Using the constructed HLA-A2-peptide tetramer to detect the HBV/HCV-specific CTL, the HBV-specific CD8(+) frequencies were 1.84% and 0.02% - 0.68% of the total CD8(+) T cells in acute and chronic HBV hepatitis, respectively. As an additional control, an HLA-A2/HCV tetramer was tested in the acute and chronic HBV hepatitis. The frequencies never exceeded 0.02% of the total CD8(+) T cell number. Similar low levels of background staining were also detected in the HLA-A2(+) or A2(-) healthy control. The HCV-specific CD8(+) frequency was 0.02 - 0.72% of the total CD8(+) T cells in chronic HCV hepatitis. The same frequencies of control were detected. CONCLUSION: High-efficient expressions of HLA-A0201-BSP and beta-2m proteins lay a good foundation for further expression and purification in prokaryotic system and constructing MHC class I-peptide tetramer complexes to study the function of CTLs. Especially, using these two HBV and HCV-specific tetramer can detect the frequencies of the HBV/HCV-specific CD8(+) T cells directly in vitro.