Zhouping Tang

Treatment of post-stroke dysphagia by vitalstim therapy coupled with conventional swallowing training

To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia, a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups: conventional swallowing therapy group, VitalStim therapy group, and VitalStim therapy plus conventional swallowing therapy group. Prior to and after the treatment, signals of surface electromyography (sEMG) of swallowing muscles were detected, swallowing function was evaluated by using the Standardized Swallowing Assessment (SSA) and Videofluoroscopic Swallowing Study (VFSS) tests, and swallowing-related quality of life (SWAL-QOL) was evaluated using the SWAL-QOL questionnaire. There were significant differences in sEMG value, SSA, VFSS, and SWAL-QOL scores in each group between prior to and after treatment. After 4-week treatment, sEMG value, SSA, VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group, but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group. It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.SummaryTo investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia, a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups: conventional swallowing therapy group, VitalStim therapy group, and VitalStim therapy plus conventional swallowing therapy group. Prior to and after the treatment, signals of surface electromyography (sEMG) of swallowing muscles were detected, swallowing function was evaluated by using the Standardized Swallowing Assessment (SSA) and Videofluoroscopic Swallowing Study (VFSS) tests, and swallowing-related quality of life (SWAL-QOL) was evaluated using the SWAL-QOL questionnaire. There were significant differences in sEMG value, SSA, VFSS, and SWAL-QOL scores in each group between prior to and after treatment. After 4-week treatment, sEMG value, SSA, VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group, but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group. It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.

Superparamagnetic Iron Oxide Labeling of Neural Stem Cells and 4.7T MRI Tracking in vivo and in vitro

Neural stem cells were labeled with superparamagnetic iron oxide (SPIO) and tracked by MRI in vitro and in vivo after implantation. Rat neural stem cells were labeled with SPIO combined with PLL by the means of receptor-mediated endocytosis. Prussian blue staining and electron microscopy were conducted to identify the iron particles in these neural stem cells. SPIO-labeled cells were tracked by 4.7T MRI in vivo and in vitro after implantation. The subjects were divided into 5 groups, including 5 × 105 labeled cells cultured for one day after labeling, 5 × 105 same phase unlabeled cells, cell culture medium with 25 μg Fe/mL SPIO, cell culture medium without SPIO and distilled water. MRI scanning sequences included T1WI, T2WI and T2*WI. R2 and R2* of labeled cells were calculated. The results showed: (1) Neural stem cells could be labeled with SPIO and labeling efficiency was 100%. Prussian blue staining showed numerous blue-stained iron particles in the cytoplasm; (2) The average percentage change of signal intensity of labeled cells on T1WI in 4.7T MRI was 24.06%, T2WI 50.66% and T2*WI 53.70% respectively; (3) T2 of labeled cells and unlabeled cells in 4.7T MRI was 516 ms and 77 ms respectively, R2 was 1.94 s−1 and 12.98 s−1 respectively, and T2* was 109 ms and 22.9 ms, R2* was 9.17 s−1 and 43.67 s−1 respectively; (4) Remarkable low signal area on T2WI and T2*WI could exist for nearly 7 weeks and then disappeared gradually in the left brain transplanted with labeled cells, however no signal change in the right brain implanted with unlabeled cells. It was concluded that neural stem cells could be labeled effectively with SPIO. R2 and R2* of labeled cells were increased obviously. MRI can be used to track labeled cells in vitro and in vivo.

Experimental Study of Cell Migration and Functional Differentiation of Transplanted Neural Stem Cells Co-labeled with Superparamagnetic Iron Oxide and Brdu in an Ischemic Rat Model

OBJECTIVE To explore the migration of transplanted neural stem cells co-labeled with superparamagnetic iron oxide (SPIO) and bromodeoxyuridine (Brdu) using the 4.7T MR system and to study the cell differentiation with immuno-histochemical method in ischemic rats. METHODS Rat neural stem cells (NSCs) co-labelled with SPIO mediated by poly-L-lysine and bromodeoxyuridine (BrdU) were transplanted into the unaffected side of rat brain with middle cerebral artery occlusion (MCAO). At weeks 1, 2, 3, 4, 5, and 6 after MCAO, migration of the labelled cells was monitored by MRI. At week 6, the rats were killed and their brain tissue was cut according to the migration site of transplanted cells indicated by MRI and subjected to Prussian blue staining and immunohistochemical staining to observe the migration and differentiation of the transplanted NSCs. RESULTS Three weeks after transplantation, the linear hypointensity area derived from the migration of labelled NSCs was observed by MRI in the corpus callosum adjacent to the injection site. Six weeks after the transplantation, the linear hypointensity area was moved toward the midline along the corpus callosum. MRI findings were confirmed by Prussian blue staining and immunohistochemical staining of the specimen at week 6 after the transplantation. Flourescence co-labelled immunohistochemical methods demonstrated that the transplanted NSCs could differentiate into astrocytes and neurons. CONCLUSION MRI can monitor the migration of SPIO-labelled NSCs after transplantation in a dynamical and non-invasive manner. NSCs transplanted into ischemic rats can differentiate into astrocytes and neurons during the process of migration.

Aggressive Blood Pressure Lowing Therapy in Patients with Acute Intracerebral Hemorrhage is Safe: A Systematic Review and Meta-analysis.

Background: The influence of blood pressure (BP) lowering on intracerebral hemorrhage (ICH) patients is unclear. To assess the safety and efficacy of aggressive antihypertensive therapies in acute ICH patients, we carried out a systematic review and meta-analysis. Methods: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and VIP database up to July 2014 were searched. High-quality randomized controlled trials were included. Low-quality trials were excluded. Serious adverse events were defined as the primary outcome. The secondary outcomes were hematoma enlargement (HE) at 24 h after onset, mortality, and favorable clinical outcome at 90 days. Results: Four high-quality trials involving a total of 1427 patients met the inclusion criteria and were analyzed. Odds ratios (ORs) of primary outcome was 0.96 (95% confidence interval [CI ]: 0.82–1.13, P = 0.61). ORs of HE at 24 h after onset, mortality and favorable clinical outcome at 90 days were 0.91 (95% CI: 0.72–1.17, P = 0.47), 0.97 (95% CI: 0.79–1.20, P = 0.81), 1.13 (95% CI: 0.98–1.30, P = 0.09) respectively. Conclusions: Aggressive BP management policies are safe and might have a potency of reducing HE and improving clinical outcome.

Generation of Neurospheres from Human Adipose-Derived Stem Cells

Transplantation of neural stem cells (NSCs) to treat neurodegenerative disease shows promise; however, the clinical application of NSCs is limited by the invasive procurement and ethical concerns. Adipose-derived stem cells (ADSCs) are a source of multipotent stem cells that can self-renew and differentiate into various kinds of cells; this study intends to generate neurospheres from human ADSCs by culturing ADSCs on uncoated culture flasks in serum-free neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF); the ADSCs-derived neurospheres were terminally differentiated after growth factor withdrawal. Expression of Nestin, NeuN, MAP2, and GFAP in ADSCs and terminally differentiated neurospheres was shown by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry; cell proliferation in neurospheres was evaluated by cell cycle analyses, immunostaining, and flow cytometry. These data strongly support the conclusion that human ADSCs can successfully differentiate into neurospheres efficiently on uncoated culture flasks, which present similar molecular marker pattern and proliferative ability with NSCs derived from embryonic and adult brain tissues. Therefore, human ADSCs may be an ideal alternative source of stem cells for the treatment of neurodegenerative diseases.

Combined Transplantation of Neural Stem Cells and Olfactory Ensheathing Cells Improves the Motor Function of Rats with Intracerebral Hemorrhage

OBJECTIVE To investigate the effects of combined transplantation of neural stem cells (NSC) and olfactory ensheathing cells (OEC) on the motor function of rats with intracerebral hemorrhage. METHODS In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC (from embryos of Wistar rats) or normal saline were injected into hematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. RESULTS The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation (P < 0.05). The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation (P < 0.05), while the difference for the NSC-OEC group was significant in 14 days after operation (P < 0.05). Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. CONCLUSION Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor function of rats with intracerebral hemorrhage.

Efficient Generation of Neural Stem Cell-Like Cells from Rat Adipose Derived Stem Cells After Lentiviral Transduction with Green Fluorescent Protein

Neural stem cells (NSCs) can be isolated from nervous tissues or derived from embryonic stem cells. However, their procurement for clinical applications is limited, and there is a need for alternative types of cell that have NSCs properties. In the present study, the differentiation potential of rat adipose-derived stem cells (ADSCs) was evaluated by infecting these cells with a lentiviral vector-encoding green fluorescent protein (GFP). ADSCs transduced with lentivirus were able to generate NSC-like cells, without any effects on their growth, phenotype, and normal differentiation potential. NSC-like cells derived from ADSCs formed neurospheres and expressed high levels of the neural progenitor marker nestin. In the absence of selected growth factors, these neurospheres differentiated into neurons expressing NeuN and MAP2 and GFAP-expressing glia, as determined by immunocytochemistry, Western blotting, and quantitative real-time polymerase chain reaction. These results demonstrate that ADSCs can be induced to generate neurospheres that have NSC-like properties and may thus constitute a potential source of cells in stem cell therapy for neurological disorders.

The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

BACKGROUND Schizophrenia is a severe psychiatric disorder with a high heritability. A single nucleotide polymorphism (SNP) rs1625579 (G/T; T is the common and presumed risk allele) within an intron of miR-137 gene has been recently suggested to contribute to the susceptibility to schizophrenia by a large-scale genome-wide association study (GWAS) in a sample of predominantly European ancestry. However, subsequent genetic association studies in Chinese population yielded inconsistent results. METHODS A meta-analysis reporting the association between rs1625579 and schizophrenia in Chinese population was carried out, pooling 4 eligible case-control studies involving 2847 patients and 3018 controls. RESULTS This meta-analysis demonstrated a significant association between rs1625579 and schizophrenia under the allele model [T versus G, odds ratio (OR):1.20, 95% confidence interval (CI): 1.06-1.36] and the recessive model (TT versus GT+GG; OR: 1.19; 95% CI: 1.04-1.37). Additionally, a marginal significant association under the additive model (TT versus GG; OR: 1.64; 95% CI: 1.00-2.69) was observed. However, no significant association was observed under the dominant model (TT+GT versus GG; OR: 1.58; 95% CI: 0.97-2.59). CONCLUSIONS This meta-analysis suggested that the SNP rs1625579 in miR-137 gene might be involved in schizophrenia susceptibility in Chinese Han population.

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10–16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.SummaryThe study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10–16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

Pneumocephalus following the minimally invasive hematoma aspiration and thrombolysis for ICH.

Abstract Introduction. The objective of this study was to clarify whether pneumocephalus occurred and affected the outcome following minimally invasive hematoma aspiration and thrombolysis for intracerebral hemorrhage (ICH). Materials and methods. A prospective case note review on all ICH patients treated with the micro-invasive procedure presenting to our division from 2006 to 2011 was conducted. Demographic, clinical, and outcome data were documented; head CT scans were applied postoperatively to identify the intracranial air collection. The ICH victims with pneumocephalus were included into Group A and the others into Group B. A multi-variant analysis was performed between Groups A and B to examine the effect of pneumocephalus on the prognosis. Results. Data were collected on a total of 134 cases in this study, among whom 72.38% developed pneumocephalus postoperatively. No significant difference was demonstrated in terms of the preoperative and postoperative hematoma volume, Glasgow Coma Scale (GCS) score, middle line shift (MLS), and 30-day mortality rate between Groups A and B, respectively. Moreover, the long-term outcome rated by GCS of these two groups was also similar. Logistic regression analysis indicated double-needle puncture be an independent risk factor for both postoperative pneumocephalus (OR, 2.478; 95% CI, 1.010–6.080; P = 0.045) and its degree (OR, 11.84; 95%CI, 4.141–30.208; P < 0.001). Conclusion: The present study shows that pneumocephalus is common following the minimally invasive hematoma aspiration and thrombolysis for ICH but may not affect the outcome. And double-needle puncture may be the risk factor for pneumocephalus.