[Mobilization of Bone Marrow Mesenchymal Stem Cells Inhibits TGF-ß Non-classical Pathway Against Myocardial Fibrosis in Rats].

OBJECTIVE: To observe the relationship between the mechanism of bone marrow stem cell mobilization mediated the myocardial fibrosis inhibition in rats and the non-classical pathway mediated by transforming growth factor-ß (TGF-ß). METHODS: Twenty two Wistar rats were subcutaneously injected with isoproterenol (Iso) to establish the model of myocardial fibrosis, and then were randomly divided into control group and granulocyte colony-stimulating factor (G-CSF)-treat group (GT group). The rats in GT group were subcutaneously injected with recombinant human granulocyte stimulating factor for 5 days, and the control group was injected with normal saline. After 4 weeks, the myocardial structure was observed by pathological staining, the content of serum B type natriuretic peptide (BNP) was detected by ELISA , the expression of type Ⅲ collagen was detected by immunohistochemistry staining and the protein expression level of typeⅠcollagen, TGF-ß, transforming growth factor kinase 1 (TAK1), mitogen-activated protein kinase kinase (MKK) and p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot. RESULTS: Compared with the control group, the serum BNP level, Masson staining collagen deposition, collagen area ratio and the expression of typeⅠcollagen, TGF- ß, TAK1, MKK3 and p38MAPK in the GT group were lower than those in the control group. CONCLUSION: Bone marrow stem cell mobilization can alleviate the degree of myocardial fibrosis in rats, which is related to the inhibition of TGF- ß/TAK1/MKK/p38MAPK pathway.

Vulnerability for apoptosis in the hippocampal dentate gyrus of STZ-induced diabetic rats with cognitive impairment.

BACKGROUND: Hyperglycemia impaired hippocampal network via triggering suicide program of immanent neurons, this is regarded as an etiological factor for diabetic cognition deficits. AIM: To investigate the occurrence of apoptosis in the hippocampal dentate gyrus of streptozotocin (STZ)-induced diabetic rats with cognitive impairment and assess the gene and protein expression of the apoptotic proteins bax, bcl-2, and caspase-3. MATERIALS AND METHODS: Four weeks after the verification of STZ-induced diabetes, diabetic rats with and without cognitive decline subgroups were subsequently assigned according to Morris water maze test. The expression levels of apoptotic proteins were measured using real-time RT-PCR and western blotting, respectively. Neuronal apoptosis was detected by TUNEL staining and electron microscopy. RESULTS: In the dentate gyrus of the rats with cognitive decline, Bcl-2 exhibited lower gene and protein levels, whereas a higher expression of bax was detected contributing to a significant increase in their mean bax/bcl-2 ratio. However, caspase-3 was not activated. Statistically different numbers of TUNEL-staining cells and features of apoptosis were no found. CONCLUSIONS: The higher bax/bcl ratio probably represents neurons of dentate gyrus vulnerable to apoptosis in the diabetes with cognitive decline. However, the normal caspase-3 level suggests that apoptosis is not active in this illness phase.

LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses.

BACKGROUND: Evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction. The low-density lipoprotein receptor (LDLR) is well-known for its role in regulating cholesterol metabolism. Whether LDLR involved in this impaired cognition and the potential mechanisms that underlie this impairment are unknown. METHODS: Twelve-month-old Ldlr-/- mice (n = 10) and wild-type littermates C57BL/6 J (n = 14) were subjected to the Morris water maze test. At 1 week after completion of the behavioural testing, all of the animals were sacrificed for analysis of synaptic and apoptotic markers. RESULTS: The plasma cholesterol concentration of Ldlr-/- mice was increased moderately when compared with C57BL/6 J mice (P < 0.05). Behavioural testing revealed that Ldlr-/- mice displayed impaired spatial memory, and moreover, the expression levels of synaptophysin and the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and dentate gyrus were decreased (all P < 0.05). Ultrastructural changes in the dentate gyrus were observed using transmission electron microscopy. Furthermore, apoptosis in the hippocampus of Ldlr-/- mice was revealed based on elevation, at both the mRNA and protein levels, of the ratio of Bax/Bcl-2 expression (all P < 0.05)and an increase in activated-caspase3 protein level (P < 0.05). CONCLUSION: LDLR deficiency contributes to impaired spatial cognition. This most likely occurs via negative effects that promote apoptosis and synaptic deficits in the hippocampus.

Corrigendum: Aberrant Interhemispheric Functional Connectivity in Diabetic Retinopathy Patients.

[This corrects the article DOI: 10.3389/fnins.2021.792264.].

Aberrant Interhemispheric Functional Connectivity in Diabetic Retinopathy Patients.

Background: Accumulating lines of evidence demonstrated that diabetic retinopathy (DR) patients trigger abnormalities in brain's functional connectivity (FC), whereas the alterations of interhemispheric coordination pattern occurring in DR are not well understood. Our study was to investigate alterations of interhemispheric coordination in DR patients. Methods: Thirty-four DR individuals (19 males and 15 females: mean age: 52.97 ± 8.35 years) and 37 healthy controls (HCs) (16 males and 21 females; mean age: 53.78 ± 7.24 years) were enrolled in the study. The voxel-mirrored homotopic connectivity (VMHC) method was conducted to investigate the different interhemispheric FC between two groups. Then, the seed-based FC method was applied to assess the different FCs with region of interest (ROI) in the brain regions of decreased VMHC between two groups. Results: Compared with HC groups, DR groups showed decreased VMHC values in the bilateral middle temporal gyrus (MTG), lingual/calcarine/middle occipital gyrus (LING/CAL/MOG), superior temporal gyrus (STG), angular (ANG), postcentral gyrus (PosCG), inferior parietal lobule (IPL), and precentral gyrus (PreCG). Meanwhile, altered FC includes the regions of auditory network, visual network, default mode network, salience network, and sensorimotor network. Moreover, a significant positive correlation was observed between the visual acuity-oculus dexter (OD) and zVMHC values in the bilateral LING/CAL/MOG (r = 0.551, p = 0.001), STG (r = 0.426, p = 0.012), PosCG (r = 0.494, p = 0.003), and IPL (r = 0.459, p = 0.006) in DR patients. Conclusion: Our results highlighted that DR patients were associated with substantial impairment of interhemispheric coordination in auditory network, visual network, default mode network, and sensorimotor network. The VMHC might be a promising therapeutic target in the intervention of brain functional dysfunction in DR patients.

A Single-Center Experience of Endovascular Treatment in Subtypes of Basilar Artery Occlusion: Embolization Caused by Tandem Vertebral Artery Stenosis May Be Associated with Better Outcomes.

OBJECTIVE: Basilar artery occlusion (BAO) is a severe condition with high mortality. However, surgical procedures and outcomes of BAO with different pathologic subtypes have not been fully clarified. This study compared the surgical procedures and clinical outcomes of mechanical thrombectomy in different subtypes of BAO. METHODS: Eighty-six patients with acute BAO receiving endovascular treatment between October 2015 and July 2019 were retrospectively analyzed and placed in 3 groups: pure embolism (group 1), arterial-arterial embolism from steno-occlusion of the tandem vertebral artery (group 2), and in situ atherosclerotic thrombosis (group 3). Recanalization rates, procedure times, surgical characteristics, and clinical outcomes were analyzed. RESULTS: Groups 1, 2, and 3 included 33 (38.4%), 17 (19.8%), and 36 (41.9%) patients, respectively. The overall successful recanalization rate was 95.3%, and the good outcome rate was 61.6%. The procedure time in group 1 was shorter than the time in groups 2 and 3 (P < 0.001). The clinical good outcome rate was higher in group 2 than in group 1 (88.2% vs. 54.5%; P = 0.017). Groups 1 and 3 had similar good outcome rates (54.5% vs. 55.6%; P = 0.933). Twenty-seven patients received stent angioplasty: 10 of 17 in group 2 (58.8%) and 17 of 36 in group 3 (47.2%). CONCLUSIONS: The outcome of endovascular treatment for BAO varies among patients with different pathologic mechanisms. Patients with embolism from tandem vertebral artery steno-occlusion achieved the best outcomes. Rescue treatment was more common in patients with embolic BAO with tandem vertebral artery steno-occlusion and BAO with in situ atherosclerotic thrombosis.

Mechanical Thrombectomy Outcome Predictors in Stroke Patients with M2 Occlusion: A Single-Center Retrospective Study.

BACKGROUND: Mechanical thrombectomy (MT) has demonstrated benefit in patients with acute ischemic stroke due to proximal large-vessel occlusion. However, it is unclear whether these results can be extrapolated to patients with an occlusion of the second segment (M2) of the middle cerebral artery (MCA). We sought to study outcomes in patients with M2 occlusion treated with MT and to better understand clinical predictors of these outcomes. METHODS: We performed a single-center retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent stent retriever MT. We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: Thirty-seven patients were included in the analysis (median admission National Institutes of Health Stroke Scale [NIHSS] score, 15 [12-19], mean age 74 [67-80] years, 48.6% women). Good clinical outcome at 3 months (modified Rankin Scale ≤2) was achieved in 48.6% of patients. Baseline NIHSS was a predictor of clinical outcomes, based on modified Rankin Scale distribution at 3 months after MT (P = 0.015, odds ratio 1.63, 95% confidence interval 1.01-2.43). CONCLUSIONS: The results of our single-institution experience suggest that MT-based endovascular therapy for M2 occlusions is safe and effective. Baseline NIHSS was a predictor of outcomes in patients treated with MT for M2 segment occlusion of the MCA.

Mechanical Thrombectomy Using Solitaire in Acute Ischemic Stroke Patients with Vertebrobasilar Occlusion: A Prospective Observational Study.

BACKGROUND: The safety and effectiveness of endovascular mechanical thrombectomy in patients with acute vertebrobasilar occlusion (VBO) are debatable and undergoing evaluation. We report the clinical outcome and prognostic factors in a prospective cohort of acute ischemic stroke patients with VBO. METHODS: In total, 48 consecutive patients with acute VBO underwent mechanical thrombectomy using Solitaire. We analyzed clinical and imaging data and searched for predictors of good clinical outcome (modified Rankin scale score: 0-3). RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale score was 22.0. The median duration from symptom onset to recanalization was 493.5 minutes. A total of 35.4% of the patients received rescue therapy. Recanalization (modified Thrombolysis In Cerebral Infarction: 2b-3) was successful in all patients. Clinically relevant intracranial hemorrhage was observed in 2 patients. After 90 days, good outcomes were obtained in 27 patients. The baseline National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS), anesthesia type, and posterior communicating artery (PComA) patency were significantly associated with outcomes at 90 days in univariate analysis. Multivariate logistic regression indicated that high pc-ASPECTS at admission and PComA patency were independent predictors of good outcome at 90 days. CONCLUSIONS: Up to 60.4% of the patients reached good outcomes after endovascular treatment and 35.4% of the patients received rescue therapy, suggesting that mechanical thrombectomy using Solitaire in patients with stroke with VBO is safe and effective and that rescue therapy is readily required and employed. High baseline pc-ASPECTS and PComA patency were associated with better outcomes after thrombectomy in these patients.

Optimal target range for blood glucose in hyperglycaemic patients in a neurocritical care unit.

BACKGROUND: Hyperglycaemia is common among patients with critical neurological injury, even if they have no history of diabetes. The optimal target range for normalizing their blood glucose is unknown. METHODS: Retrospective data were extracted from 890 hyperglycaemic individuals (glucose > 200 mg/dL) admitted to neuroscience critical care unit (NCCU) and these patients were divided into two groups: intensive glucose control group with target glucose of < 140 mg/dL achieved and moderate control with glucose levels 140-180 mg/dL. The groups were also stratified according to the hyperglycaemia type (pre-existing diabetes or stress-related). We defined the primary endpoint as death from any cause during NCCU admission. RESULTS: In NCCU, tighter control of blood glucose at ≤ 140 mg/dL was associated with increased, mortality of individuals with pre-existing diabetes compared with moderate control [29 of 310 patients (9.4%) vs 15 of 304 patients (4.9%), p = 0.034]. Patient age [adjusted odds ratio (OR) = 1.12; 95% confidence interval (CI) = 1.05-1.19; p < 0.001], level of glycated haemoglobin (adjusted OR = 1.24; 95% CI = 1.04-1.48; p = 0.017) and hypoglycaemia (adjusted OR = 10.3; 95% CI = 2.92-36.6; p < 0.001) were positively associated with higher mortality. Death rate was lower among stress-related hyperglycaemic patients with tighter glucose controlled at ≤ 140 mg/dL [6 of 140 patients (4.3%) vs 15 of 136 patients (11.0%), p = 0.035]. CONCLUSION: A differential association is evident between glucose levels and mortality in diabetes and stress-related hyperglycaemia patients. However, given the observational nature of our work, no clinical recommendations can be given and prospective studies are required to further investigate these findings.

Prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in a Chinese hospital.

BACKGROUND: Accumulating evidence indicates that dyslipidaemia plays an important role in the progression of kidney disease in patients with diabetes. Hyperlipidaemia is a risk factor for microalbuminuria in patients with diabetes. Little information exists on the prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in China. The aims of this study were to investigate the prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in a Chinese hospital as well as factors affecting the disease. METHODS: A total of 1060 type 2 diabetic inpatients were assigned to the with-microalbuminuria group (n = 635) or the without-microalbuminuria group on the basis of urinary albumin-to-creatinine ratios (UACRs = 30-299 mg/g). Serum levels and the control of lipid profiles were assessed and classified according to the 2011 American Diabetes Association (ADA) guidelines, and low-density lipoprotein-cholesterol (LDL-C) was also assessed and classified according to Chinese intensified control criteria. Multiple regression analyses were performed to examine the factors affecting lipid variables. RESULTS: Among patients with microalbuminuria, a significantly lower prevalence was found (33.1% vs. 58.6%; 35.3% vs. 52.5%, all p < 0.001) at target levels [LDL-C < 2.60 mmol/L or high-density lipoprotein-cholesterol (HDL-C) > 1.0 mmol/L for men and >1.3 mmol/L for women]. According to the intensified LDL-C goal (<2.07 mmol/L), a lower prevalence was found in male patients (15.5% vs. 32.7%, p < 0.001). Fewer patients with microalbuminuria were adherent to the therapy prescribed for dyslipidaemia (28.8% vs. 43.3%, p < 0.001). Even among patients who were on lipid-lowering treatment, the majority of individuals remained uncontrolled for all three lipid fractions [LDL-C, HDL-C and triglyceride (TG)] (82.5% vs. 69.0%, p = 0.003). Lipid and lipoprotein parameters were associated with gender and age. CONCLUSION: In China, diabetic patients with microalbuminuria displayed typical dyslipidaemias and were not adequately controlled. Intensified LDL-C and overall lipid-lowering clinical goals are potential precautions taken against diabetic nephropathy.

Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis.

OBJECTIVE: Randomised controlled trials (RCTs) indicate that statin therapy has cardiovascular benefit among patients with type 2 diabetes. Recently, statins were reported to increase risk of diabetes by 9%. The aim was to investigate by a meta-analysis whether statins deteriorate glycaemic control in type 2 diabetes. METHODS: Medline, EMBASE and Cochrane Central Register of Controlled Trials from 1966 to 2012 were searched for RCTs of statins. Included were only trials with type 2 diabetes. MAIN OUTCOME MEASURES: The I(2) statistic was used to measure heterogeneity between trials and calculated mean differences for glycaemic parameters with random-effect meta-analysis. RESULTS: 26 eligible studies were identified with 3232 participants. Statin therapy had no remarkable influence on HbA1c (WMD 0.04%, 95% CI -0.08 to 0.16, I² = 45.7%, n = 3070), FPG (2.25 mg/dl, 95% CI -3.50 to 7.99, I² = 46%, n = 1176), BMI, fasting insulin or HOMA-IR. However, subgroup analysis showed significant, detrimental effect of atorvastatin on HbA1c, whereas simvastatin presented an ameliorative effect. Meta-regression presented that neither baseline age nor relative reduction in LDL-cholesterol concentrations accounted for residual heterogeneity. CONCLUSION: Statin therapy showed non-significant effect on glycaemic control in type 2 diabetes. Statin therapy need not change among them with moderate or high cardiovascular risk or existing cardiovascular disease.