Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1.

INTRODUCTION: Recessive mutations in the CAPN3 gene can lead to limb-girdle muscular dystrophy recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. METHODS: We performed targeted next-generation sequencing of all exons of the CAPN3 gene in 4 patients with sporadic limb-girdle muscular dystrophy (LGMD) and further analyzed the effects of the novel identified variant using various software tools. RESULTS: We found 5 variants in CAPN3 gene in 4 patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. DISCUSSION: Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium-pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

Total magnetic resonance imaging of cerebral small vessel disease burden predicts dysphagia in patients with a single recent small subcortical infarct.

BACKGROUND: This study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI). METHODS: We retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4. RESULTS: In total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level. CONCLUSIONS: Dysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

A New Nomogram Model for Individualized Prediction of Cognitive Impairment in Patients with Acute Ischemic Stroke.

BACKGROUND: Cognitive impairment is a common symptom after ischemic stroke. Such symptom can cause effect on rehabilitation of patients and their quality of life and. As stroke rapidly growth on nowadays, a reliable scoring tool to detect the risk of cognitive impairment after stroke is now being put on the first place. METHODS: We enrolled patients with acute ischemic stroke (AIS) as samples and hospitalized all at the First Affiliated Hospital of Soochow University between October 2018 and June 2020. All patients were assessed by the Montreal Cognitive Assessment (MoCA) scales and MoCA score < 26 was defined as standard to have having cognitive impairment. All patients were randomly (7:3) divided into two cohorts: the primary ones and the validated ones. Based on multivariate logistic model, the independent predictors of cognitive impairment in the acute phase were identified. The predictive nomogram was generated and evaluated by Harrell's concordance index (C-index) and calibration plot both in two cohorts, respectively. RESULTS: A total of 191 patients were enrolled, of whom 135 comprised the primary cohort and 56 comprised the validated cohort. Gender, age, baseline NIHSS score, hyperhomocysteinemia (HHcy) and multiple lesions were independently associated with acute cognitive impairment after stroke and included to construct the nomogram. The nomogram derived from the primary cohort had an Area Under Curve (AUC) of 0.773 and the validated ones had an AUC of 0.859. Calibration plot revealed adequate fit of the nomogram in predictive value. CONCLUSION: The new nomogram based on gender, age, baseline NIHSS score, HHcy and multiple lesions gave rise to an accurate and comprehensive prediction for cognitive impairment in AIS patients. After further validation, it could potentially be a reliable forecasting tool.

Effects of repetitive transcranial magnetic stimulation combined with transcranial direct current stimulation on motor function and cortex excitability in subacute stroke patients: A randomized controlled trial.

OBJECTIVE: To explore effects of repetitive transcranial magnetic stimulation (rTMS) combined with transcranial direct current stimulation (tDCS) on motor function and cortex excitability in subacute stroke patients. DESIGN: Randomized controlled trial. SETTING: Inpatient hospitals. SUBJECTS: Sixty-five participants were randomly assigned to four groups: sham, 1Hz rTMS, cathodic tDCS combined with 1Hz rTMS (tDCS-/rTMS-) and anodic tDCS combined with 1Hz rTMS (tDCS+/rTMS-). INTERVENTIONS: Four interventions were used, including sham, 1Hz rTMS, and cathodal or anodal tDCS, followed by 1Hz rTMS over contralesional motor cortex, which continued for four weeks. MAIN MEASURES: Outcome measures were motor function and cortical excitability, evaluated by Fugl-Meyer Assessment, National Institutes of Health Stroke Scale and Barthel Index, resting Motion Threshold, Motor Evoked Potentials and Central Motor Conduction Time, assessed at baseline, four weeks and eight weeks. RESULTS: At four weeks after interventions, Fugl-Meyer Assessment lower limb change score in tDCS+/rTMS- group was significantly larger than other three groups (P < 0.001). There were significant differences in bilateral Motor Evoked Potentials changes between tDCS+/rTMS- group and sham group (P < 0.05). At eight weeks, compared to other groups, National Institutes of Health Stroke Scale (P = 0.003), Barthel Index (P = 0.002), FMA lower limb score (P < 0.001), and bilateral resting Motion Threshold, Motor Evoked Potentials (P < 0.05) showed significant changes in tDCS+/rTMS- group. Furthermore, Fugl-Meyer Assessment lower limb change score was associated with increased ipsilesional Motor Evoked Potentials (r = 0.703 P < 0.001) in tDCS+/rTMS- group. CONCLUSION: 1Hz rTMS combined with anode tDCS stimulation protocol could be a preferable rehabilitative strategy for motor recovery in subacute stroke patients.

A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients.

BACKGROUND: A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA). METHODS: We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot. RESULTS: A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score ≥ 13, and onset-to-treatment time (OTT) ≥ 180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221-0.9904, P < 0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores. CONCLUSIONS: This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score ≥ 13, and OTT ≥ 180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.

Value of thrombus imaging in predicting the outcomes of patients with large-vessel occlusive strokes after endovascular therapy.

BACKGROUND: Acute ischemic stroke leads to serious long-term disability and high mortality, especially in patients with large-vessel occlusive strokes. Nowadays, endovascular therapy is considered as an alternative treatment for these patients. Several studies have used thrombus characteristics based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) to predict prognosis in ischemic stroke. We conducted a systematic review to identify potential imaging predictive factors for successful recanalization and improved clinical outcome after endovascular therapy in patients with large-vessel occlusion (LVO) in anterior arterial circulation. METHODS: The PubMed databases were searched for related studies reported between September 18, 2009, and September 18, 2019. RESULTS: We selected 11 studies on revascularization and 12 studies on clinical outcome. Patients with thrombus of higher Hounsfield unit (HU), shorter length, higher clot burden score, and increased thrombus permeability may achieve higher recanalization and improved clinical outcome, but the matter is still under debate. CONCLUSION: Imaging of thrombus can be used as an aseessment tool to predict the outcomes and it needs further studies in the future.

The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment.

BACKGROUND AND PURPOSE: Various types of cerebral small vessel diseases (CSVD) are commonly coexisting and the clinical outcome possibly is determined by their combined effect. The present study was designed to explore the possible relationship between the global burden of CSVD and clinical outcomes after recombinant tissue plasminogen activator (rt-PA) treatment of ischemic stroke. METHODS: We enrolled patients with acute ischemic stroke (AIS) after IV rt-PA treatment between August 2016 and July 2018. According to the total burden rating scale of CSVD, we calculated the total CSVD score for white matter hyperintensities, lacunar infarction, cerebral microbleeds, and perivascular spaces. All patients were assessed on the basis of the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score at 90 days after stroke. We used multivariate logistic regression analysis to examine the associations between global burden of CSVD and degree of neurological deficit and clinical outcomes. ROC curve analysis was used to determine cut-off values of the total CSVD score in predicting poor outcomes. RESULTS: The results showed that the total CSVD score was independently associated with moderate to severe stroke (OR 2.187, 95%CI 1.495-3.119, P < 0.001). Initial NIHSS (OR 1.23, 95%CI 1.144-1.330, P < 0.001), OTT (OR 1.007, 95%CI 1.000-1.014, P = 0.037), and CSVD score (OR 3.157, 95%CI 2.120-4.703, P < 0.001) was significantly related to poor functional outcome at 3 months. The total CVSD score cut-off value of 1.5 was determined at best to distinguish between good prognosis and poor outcome (AUC 0.7534 [95%CI 0.6883-0.8185]). CONCLUSIONS: The global burden of CSVD was independently associated with neurological deficit severity and clinical outcomes of AIS after IV rt-PA treatment. The total CVSD score is a reliable predictor for poor outcomes of AIS after IV rt-PA treatment.

Renal Dysfunction Associated with Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis.

BACKGROUND AND AIM: Renal dysfunction (RD) is prevalent in patients with acute ischemic stroke requiring intravenous thrombolysis. The relationship between renal function and thrombolysis related intracranial hemorrhagic (ICH) complications is contradictory according to previous studies. The current study is to clarify whether RD could increase the risk of symptomatic intracranial hemorrhage (SICH) after recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke patients. METHODS: In this observational study, acute ischemic stroke patients who received IV rtPA within 4.5 hours of symptom onset were retrospectively analyzed. Creatinine levels on admission served to calculate glomerular filtration rate (GFR) to estimate RD. SICH was defined with National Institute of Neurological Disorder and Stroke (NINDS, SICHNINDS) or European Cooperative Acute Stroke Study II (ECASS II, SICHECASSII) criteria. Association of RD with SICH was assessed using continuous GFR or binary GFR (RD defined as GFR < 90 ml/minute/1.73 m2). RESULTS: Of 312 patients included, the incidence of SICHNINDS was 7.69%, of SICHECASSII was 5.45%. Patients with RD had higher prevalence of SICHNINDS (12.80% versus 2.03%, P < .001) and SICHECASS II (9.15% versus 1.35%, P = .002). GFR as a continuous variable was associated with SICHNINDS (ORadjust = .97, P = .003), but not with SICHECASS II. GFR less than 90 ml/minute/1.73 m2 remained independently associated with SICHNINDS (ORadjust = 4.79, P = .016), and SICHECASS II (ORadjust = 2.99, P = .032) in multiple logistic regression analysis. CONCLUSIONS: Renal function is independently associated with SICH after IV rtPA thrombolysis. RD is an independent predictor for both SICHNINDS and SICHECASS II. RD should be considered when evaluating the risk of intravenous thrombolysis with IV rtPA.

Association of GPIa and COX-2 gene polymorphism with aspirin resistance.

OBJECTIVE: This study aimed to explore the association between GPIa, COX-2 gene polymorphisms and aspirin resistance in the ischemic stroke patients from the southern part of Jiangsu province. METHODS: In all, 97 patients with acute ischemic stroke were enrolled in the study. GPIa gene polymorphism at 807C>T (rsl126643) locus and COX-2 gene polymorphism at -765G>C (rs20417) locus were genotyped by PCR pyrosequencing technology. Patients were divided into the aspirin sensitivity (AS) group and aspirin resistance (AR) group according to the platelet aggregation rate. The relationship between the two gene polymorphisms and aspirin resistance was investigated and analyzed. RESULTS: The distribution of the genotype (CC, CT, TT, CT + TT, and CC) and the frequency of allele T of GPIa gene at 807C>T locus were significantly different in AS and AR groups in female patients (P < .05). Logistic regression analysis showed that the genotype of CT+TT at 807C>T locus was significantly correlated with AR after adjustment for relative factors (P = .047, OR = 4.856, 95% CI: 1.020-23.108). There were no significant differences in the genotype distribution and allele frequency of the COX-2 gene -765G>C site between two groups (P > .05). CONCLUSION: GPIa gene polymorphism at 807C>T locus was associated with AR in Chinese Han females, and the expression of allele T increased the incidence of AR. The gene polymorphism of COX-2 gene at -765G>C locus was not significantly correlated with AR.

[Effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats].

OBJECTIVE: To investigate the effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats.
 Methods: Forty male Wistar rats (2 weeks, average weight 200 g) were randomly divided into a control group and an experimental group (n=20 per group). The experimental group received subcutaneous injections of growth hormone at a dose of 0.15 U/(kg.d), and the control group received equivalent volumes of saline. A nickel-titanium spring was fixed between the maxillary incisors and the left upper first molar with a force of 0.49 N to move the molar mesially. All rats were sacrificed on day 3, 7, 10 or 14 with cardiac perfusion. And the left side of upper jaw was removed. The longitudinal section of the first molar was prepared from sagittal direction to observe osteopontin expression in the pressure area between the mesial buccal root and distal buccal root by immunohistochemical staining and semi-quantitative analysis.
 Results: The positive expression of osteopontin in the 2 groups showed similar trend, which was increased firstly and then was decreased. The expression of osteopontin on day 7 in the experimental group showed strong positive expression but it was decreased significantly on day 10 compared with the control group (P<0.05).
 Conclusion: Systemic application of growth hormone could affect the expression of osteopontin and probably plays an important role in regulating bone resorption in the compression area during orthodontic tooth movement in rats.

Mobilization of Circulating Endothelial Progenitor Cells by dl-3-n-Butylphthalide in Acute Ischemic Stroke Patients.

OBJECTIVE: The research aim was to investigate the effects of dl-3-n-butylphthalide (NBP) on the level of circulating endothelial progenitor cells (EPCs) and clinical outcome in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: A total of 170 patients were included and randomly assigned to NBP group and control group. All patients were administrated a basic antiplatelet and lipid-lowering therapy. Among the patients, 86 received additional NBP administration for 30 days, whereas 84 received only basic therapy (the control). The level of circulating EPCs (marked with CD34(+)/CD133(+)/KDR(+)) was determined by flow cytometry at baseline and days 7, 14, and 30 after therapy. Impairment of neurological function was evaluated by the National Institutes of Health Stroke Scale (NIHSS) on days 7, 14, 30, and 90 after therapy. The association between the increased level of circulating EPCs and improvement of NIHSS score was evaluated by Pearson analysis. The clinical outcome was evaluated by modified Rankin Scale (mRS) on day 90. During the observation period, any adverse events related to drugs were reported. RESULTS: The levels of circulating EPCs on days 14 and 30 were significantly higher in the NBP group than in the control group. In contrast, NIHSS score was notably lower in NBP group on day 14, 30 and day 90. Pearson correlation analysis revealed a significant association between the increased level of EPCs and improvement of NIHSS score. Also, the mRS score in the NBP group was lower on day 90. Importantly, the reported adverse events in the 2 groups were comparable. CONCLUSION: NBP significantly increases the circulating level and improves clinical outcome in patients with AIS.

Efficacy and safety outcomes of Tenecteplase versus Alteplase for thrombolysis of acute ischemic stroke: A meta-analysis of 9 randomized controlled trials.

BACKGROUND: In recent years, Tenecteplase (TNK), a genetically modified variant of alteplase, has been verified as a potential substitute for alteplase in the reperfusion therapy of acute ischemic stroke (AIS). Given the emergence of new randomized controlled trials (RCTs) of this subject, a meta-analysis was conducted to evaluate the present comparative evidence regarding the efficacy and safety outcomes of TNK and alteplase in thrombolysis for AIS. METHODS: Following predefined inclusion criteria, we searched the databases of PubMed, Web of Science, and Cochrane Library. RCTs satisfying our inclusion criteria were selected for meta-analysis. Outcome indicators were categorized into efficacy outcomes (early vessel recanalization, excellent recovery, good recovery and early neurological improvement) and safety outcomes (poor recovery, symptomatic intracerebral hemorrhage, parenchymal hemorrhage type 2(PH2) post thrombolysis, and mortality). We extracted data on efficacy outcomes and safety outcomes for patients with AIS in the TNK group at a dose of 0.25 mg/kg and the alteplase group at a dose of 0.9 mg/kg, and expressed the relative risks between the 2 groups as odds ratios (ORs) and 95% confidence intervals (CIs) using the Mantel-Haenszel method. For further insight, we performed a network meta-analysis using a Bayesian framework to compare different doses of TNK (0.1, 0.25, 0.32, and 0.4 mg/kg) with alteplase (0.9 mg/kg). RESULTS: A total of 2994 patients in 9 RCTs comparing efficacy and safety outcomes in patients with AIS treated with TNK and alteplase were included. In a pairwise analysis of TNK 0.25 mg/kg and alteplase 0.9 mg/kg, regarding efficacy outcomes, the aggregated results show that TNK 0.25 mg/kg statistically significant increased early vessel recanalization (N = 368, TNK vs. alteplase, OR: 2.07,95%CI: [1.19,3.59], I2 = 0%) and excellent recovery (N = 3548, TNK vs. alteplase, OR: 1.15,95%CI: [1.01,1.32], I2 = 0%). There was no significant difference in good recovery (N = 3486, TNK vs. alteplase, OR: 1.38,95%CI: [0.89,2.15], I2 = 84%) or early neurological improvement (N = 1686, TNK vs. alteplase, OR: 1.06,95%CI: [0.87,1.28], I2 = 24%) between the TNK 0.25 mg/kg group and the alteplase 0.9 mg/kg group. In the safety outcomes, pooled results showed no significant difference in poor recovery (N = 3548, TNK vs. alteplase, OR: 0.94,95%CI: [0.81,1.10], I2 = 0%) and symptomatic intracerebral hemorrhage (N = 3567, TNK vs. alteplase, OR: 1.06,95%CI: [0.70,1.60], I2 = 0%) and PH2(N = 3103, TNK vs. alteplase, OR: 1.26,95%CI:[0.39,4.07], I2 = 56%)and mortality (N = 3447, TNK vs. alteplase, OR: 0.99,95%CI: [0.80,1.23], I2 = 33%) between the TNK group and the alteplase group. In a network meta-analysis, competing treatments were not significantly different from one another (TNK 0.1 mg/kg, TNK 0.25 mg/kg, TNK 0.32 mg/kg, TNK 0.4 mg/kg, alteplase 0.9 mg/kg) in either efficacy outcomes or safety outcomes. CONCLUSION: In this analysis of 9 RCTs in patients with AIS, TNK 0.25 mg/kg was comparable to alteplase 0.9 mg/kg from the perspective of efficacy outcomes and safety outcomes after thrombolysis within 4.5 h of AIS occurrence.

A Review: Visuospatial Dysfunction in Patients with the Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) impairs visuospatial function, and this is one of the most obvious areas of cognitive impairment in CSVD. So, recognizing, monitoring, and treating visuospatial dysfunction are all important to the prognosis of CSVD. This review discussed the anatomical and pathological mechanisms, clinical recognition (scales, imaging, and biomarkers), and treatment of cognitive impairment especially visuospatial dysfunction in CSVD.

[Effects of endogenous dopamine on two-state voltage oscillations of striatum medium spiny neurons].

OBJECTIVE: To explore the effects of endogenous dopamine (DA) on striatum medium spiny neurons (MSNs) in acute brain slices by the means of electrophysiology and elucidate the impact of nigrostriatal circuit loop on the functional status of MSNs. METHODS: Various structural combinations of striatum and cortex or/and substantia nigra were used to explore the conditions with appearance of spontaneous two-state voltage oscillations. And the blockage of dopaminergic or glutamic acid receptor was employed to examine how amino glutaminic acid from cortex and dopamine from substantia nigra influenced two-state voltage oscillations. RESULTS: It was found that 65.2% (30/46) MSNs recorded in corticostriatonigral slices displayed spontaneous and two-state voltage oscillations.92.3% (24/26) of MSNs in dorsal striatum close to cortex. And the percentage was only 30% (6/20) in ventral striatum. The amplitude of depolarized plateau potential (up state) decreased through a blockage of dopamine receptor (P < 0.05). The potential level of up state decreased through a blockage of D1 receptor (P < 0.05) and action potentials were stopped. The results of blocking D2 receptors were the increased potentials level of two states (P < 0.05). The membrane potential of MSNs showed a stable resting level in corticostriatonigral (-67 ± 3 mV, n = 10), corticostriatal (-70 ± 3 mV, n = 10), striatal (-73 ± 3 mV, n = 10) and nigrostriatal (-71 ± 3 mV, n = 10) slices. There was no significant difference (P > 0.05) . CONCLUSION: Endogenous dopamine from substantia nigra may regulate the instantaneous integration and coding of information from cortex by tonic effect on short-term plasticity of paired and short pulses in corticostriatal synapses.

A Nomogram Prediction Model Based on Tissue Window for the Prognosis of Patients with Acute Ischemic Stroke Undergoing Thrombectomy.

OBJECTIVE: Thrombectomy greatly improves the clinical prognosis of patients with acute ischemic stroke (AIS). The aim of this study is to develop a nomogram model that can predict the prognosis of patients with acute ischemic stroke undergoing thrombectomy. METHODS: We retrospectively collected information of patients with acute ischemic stroke who were admitted to the stroke Green Channel of the First Affiliated Hospital of Soochow University from September 2018 to May 2022. The main outcome was defined as a three-month unfavorable outcome (modified Rankin Scale 3-6). Based on the results of multivariate regression analysis, a nomogram was established. We tested the accuracy and discrimination of our nomogram by calculating the consistency index (C-index) and plotting the calibration curve. RESULTS: National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.418; 95% CI, 1.177-1.707; P＜0.001), low density lipoprotein cholesterol (LDL-C) (OR, 2.705; 95% CI, 1.203-6.080; P = 0.016), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (OR, 0.633; 95% CI, 0.421-0.952; P = 0.028), infarct core volume (OR, 1.115; 95% CI, 1.043-1.192; P = 0.001) and ischemic penumbra volume (OR, 1.028; 95% CI, 1.006-1.050; P = 0.012) were independent risk factors for poor clinical prognosis of AIS patients treated with thrombectomy. The C-index of our nomogram was 0.967 and the calibration plot revealed a generally fit in predicting three-month unfavorable outcomes. Based on this nomogram, we stratified the risk of thrombectomy population. We found that low-risk population is less than or equal to 65 points, and patients of more than 65 points tend to have a poor clinical prognosis. CONCLUSION: The nomogram, composed of NIHSS, LDL-C, ASPECTS, infarct core volume and ischemic penumbra volume, may predict the clinical prognosis of cerebral infarction patients treated with thrombectomy.

An autoradiographic study on the pathogenesis of levodopa-induced dyskinesia: regulation of dopamine transporter by levodopa in a rat model of Parkinson's disease.

BACKGROUND: The development of abnormal involuntary movements or dyskinesia is a serious complication of L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for Parkinson's disease (PD). OBJECTIVE: To evaluate the correlation between dopamine transporter (DAT) regulated by L-DOPA and the pathogenesis of dyskinesia in PD rats. METHODS: Thirty rats were used to establish the PD model by injecting 6-hydroxydopamine into the right medial forebrain bundle. The sham surgery rats (n = 4) received 4 µl of physiological saline. Then, 19 rats in which PD has been successfully induced were randomly assigned to the L-DOPA (20 mg/kg/day; n = 15) or model (saline; n = 4) group. After 4 weeks of treatment, (131)I-N-(3-fluoropropyl)-2ß-carbomethoxy-3 ß-(4-iodophenyl)nortropane was injected into the rats, and images of DAT in the brain were acquired using a storage phosphor plate. The levels of DAT-specific radioactivity uptake in the bilateral corpora striata (left/right) were compared. RESULTS: There was no difference in DAT-specific radioactivity uptake between the bilateral corpora striata in the sham surgery rats. The images were clear and symmetrically distributed in the corpora striata. In PD model rats, the DAT-specific radioactivity uptake decreased on the lesioned side and the ratios of uptake between the corpora striata were increased. Accumulation of the radioligand on the lesioned side was sparse. In the L-DOPA group, the average ratio values were significantly increased in dyskinetic rats and reduced in nondyskinetic rats. In addition, the differences between the bilateral corpora striata were reduced in nondyskinetic rats. CONCLUSION: L-DOPA was shown to downregulate DAT in some PD model rats. That process may be involved in the pathogenesis of dyskinesia.

Astrocyte-Derived Neuronal Transdifferentiation as a Therapy for Ischemic Stroke: Advances and Challenges.

After the onset of ischemic stroke, ischemia-hypoxic cascades cause irreversible neuronal death. Neurons are the fundamental structures of the central nervous system, and mature neurons do not renew or multiply after death. Functional and structural recovery from neurological deficits caused by ischemic attack is a huge task. Hence, there remains a need to replace the lost neurons relying on endogenous neurogenesis or exogenous stem cell-based neuronal differentiation. However, the stem cell source difficulty and the risk of immune rejection of the allogeneic stem cells might hinder the wide clinical application of the above therapy. With the advancement of transdifferentiation induction technology, it has been demonstrated that astrocytes can be converted to neurons through ectopic expression or the knockdown of specific components. The progress and problems of astrocyte transdifferentiation will be discussed in this article.

Relationship between triglyceride-glucose index and carotid plaques in a high-stroke-risk population in southeast china: A population-based cross-sectional survey.

Background: Cervical arterial atherosclerosis (CAA) is an important risk factor of stroke in China. The triglyceride-glucose (TyG) index is a simple and low-cost marker for ischemic stroke. Whether the TyG index predicts cervical arterial atherosclerosis remains uncertain. This study aimed to investigate the relationship between the TyG index and cervical arterial atherosclerosis. Methods: This cross-sectional study was conducted in residents aged ≥40 years in the general population of southeast China. All participants completed a detailed questionnaire and provided blood samples. The high-stroke-risk groups further completed cervical artery ultrasonography. The TyG index was calculated using a well-established formula and analyzed in quartiles (Q1-Q4). Multivariate logistic regression was used to investigate the relationship between the TyG index and cervical arterial atherosclerosis. Results: A total of 4,499 participants aged ≥40 years were finally included, with 23.47% comprising the high-stroke-risk population. The prevalence rates of increased intima-media thickness (IMT), carotid plaque, and cervical artery stenosis (CAS) in the high-stroke-risk population were 21.97%, 39.3%, and 6.1%, respectively. Subjects with higher TyG were still more likely to have carotid plaque. After adjusting for several established risk factors, compared with the TyG-Q1 group, the TyG-Q2, TyG-Q3, and TyG-Q4 groups were more likely to have carotid plaque (OR = 1.85, 95%CI = 1.28-2.67; OR = 1.51, 95%CI = 1.05-2.18; and OR = 1.29, 95%CI = 0.90-1.84). TyG was an independent predictor of the presence of plaque in the carotid artery of the high-stroke-risk population. Conclusions: An elevated TyG index is a potential predictor of carotid plaques in the high-stroke-risk population older than 40 years.

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy.

BACKGROUND: C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. AIMS: We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. METHODS: The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. RESULTS: hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). CONCLUSIONS: hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients.