Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes.

PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.

Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.

Associations of Serum Antimicrobial Peptide LL-37 with Longitudinal Cognitive Decline and Neurodegeneration Among Older Adults with Memory Complaints.

BACKGROUND: A potential role of the antimicrobial peptide LL-37, which is upregulated after infection, in the pathogenesis of Alzheimer's disease (AD) was identified. However, the clinical relevance of LL-37 in AD is not clear yet. OBJECTIVE: This study aims to investigate the association of circulating LL-37 with longitudinal cognitive decline and neurodegeneration among older adults with memory complaints. METHODS: This cohort study recruited 357 older adults with memory complaints. Participants were followed-up for two years and the cognitive functions were assessed using the Mini-Mental State Examination (MMSE). Serum LL-37, pTau181, and tTau levels were determined at baseline. Associations of baseline LL-37 with longitudinal cognitive decline and change of neurodegenerative biomarkers were analyzed. RESULTS: No difference was found in the slope of longitudinal cognitive decline during follow-up between the low and high LL-37 group, adjusting for age, sex, education, body mass index, APOE ɛ4 carrier status, comorbidities, and baseline MMSE scores (difference in slope: 0.226, 95% CI: -0.169 to 0.621). Higher LL-37 levels were associated with longitudinal cognitive decline, as indicated by a decrease of MMSE scores of 3 points or above during follow-up (OR = 2.11, 95% CI: 1.32 to 3.38). The high LL-37 group had larger slopes of the increase in neurofilament light (difference in slope: 3.759, 95% CI: 2.367 to 5.152) and pTau181 (difference in slope: 0.325, 95% CI: 0.151 to 0.499) than the low LL-37 group. CONCLUSION: These findings support an association of the antimicrobial peptide LL-37 with AD from a clinical perspective.

Novel compound heterozygous mutations of LAMA2-limb-girdle muscular dystrophy: A case report and literature review.

The laminin α2 (LAMA2) gene pathogenic variants can lead to limb-girdle muscular dystrophy (known as LGMDR23), which is rarely reported and characterized by proximal weakness in the limbs. We present the case of a 52-year-old woman who gradually developed weakness in both lower extremities since the age of 32 years. Magnetic resonance imaging (MRI) brain showed symmetrical sphenoid wings-like white matter demyelination in bilateral lateral ventricles. Electromyography showed quadriceps muscle damage on the bilateral lower extremity. Next-generation sequencing (NGS) found two loci variations in the LAMA2 gene, i.e., c.2749 + 2dup and c.8689C>T. This case highlights the importance of considering LGMDR23 in patients presenting with weakness and white matter demyelination on MRI brain and further expands the gene variants spectrum of LGMDR23.

Helicobacter pylori Infection Is Associated with Long-Term Cognitive Decline in Older Adults: A Two-Year Follow-Up Study.

BACKGROUND: Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. OBJECTIVE: This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. METHODS: This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. RESULTS: At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEɛ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, p < 0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. CONCLUSION: H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.

Anti-CASPR2 encephalitis in a liver posttransplant patient receiving immune-suppression and lenvatinib: a case report and literature review.

It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.

Cerebral blood volume index may be a predictor of independent outcome of thrombectomy in stroke patients with low ASPECTS.

INTRODUCTION: To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) ＜6 undergoing endovascular therapy (EVT). METHODS: This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS ＜6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH. RESULTS: A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90 days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (n = 8) was higher than mRS 4-5 group (n = 14) (P＜0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (n = 5) and non-sICH group (n = 17). CONCLUSIONS: AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.

Different Doses of Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: A Network Meta-Analysis.

Background: This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a network meta-analysis (NMA). Methods: Studies comparing different doses of tPA in AIS were identified by retrieving electronic databases. NMAs of outcome measures included favorable functional outcome with a modified Rankin scale score (mRS) of 0 or 1 at 3 months after treatment (3M-FF), the functional independence with a mRS of 0, 1, or 2 at 3 months (3M-FI), symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M). Symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M) were assessed. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the best dose of tPA. Inconsistency was evaluated by node-splitting analysis and a loop-specific approach. Publication bias was analyzed by funnel plots. Results: A total of 14 studies were included in the quantitative synthesis. The NMA results revealed no difference among low (<0.7 mg/kg), moderate (0.8 mg/kg), and standard (0.9 mg/kg) doses of tPA with regard to efficacy and safety. The SUCRAs of 3M-FF and 3M-FI showed that the standard dose ranked first, the moderate dose ranked second, and the low dose ranked third. The SUCRA of sICH showed that the standard dose ranked first (78.1%), the low dose ranked second (61.0%), and the moderate dose ranked third (11.0%). The SUCRAs of 3-month mortality showed that the standard dose ranked first (73.2%), the moderate dose ranked second (40.8%), and the low dose ranked third (36.1%). No significant inconsistency was shown by node-splitting analysis and no publication bias was shown in funnel plots. Conclusion: Lower dose tPA was comparable to the standard dose with regard to efficacy and safety. Based on the SUCRA results and American Heart Association/American Stroke Association (AHA/ASA) guidelines, the standard dose was still the optimal selection for AIS.

Research on Mechanism of miR-106a Nanoparticles Carrying Dexmedetomidine in Regulating Recovery and Metabolism of Nerve Cells in Hypoxia-Reoxygenation Injury.

We studied the mechanism of miR-106a nanoparticles carrying dexmedetomidine (DEX) in regulating the recovery and metabolism of nerve cells in hypoxia-reoxygenation injury. Hippocampus neuron model in hypoxia-reoxygenation injury was prepared in vitro. Study groups were randomly divided into control set, ischemic reperfusion (IR) set, dexmedetomidine (DEX) set, miR-106a-nanoparticles (NPs) set and set of dexmedetomidine (DEX) and miR-106a-NPs. We studied miR-106a expression, proliferative and apoptotic activity, secretion of IL-6 and tumor necrosis factor (TNF)-α, quantity of Phosphocreatine (PCr), adenosine triphosphate (ATP) and total adenine nucleotide, and also content of reactive oxygen species (ROS) and superoxide dismutases (SOD). Expressions of of Bax, Bcl-2 and NF-κB were also detected. Results showed that the expression of miR-106a in hippocampus neuron was reduced, while proliferation was reduced and apoptotic activity was increased. The secretions of IL-6 and TNF-α were increased, while the quantities of Phosphocreatine (PCr), adenosine triphosphate (ATP) and total adenine nucleotide were reduced. Bax expression was also increased and Bcl-2 expression was reduced. Moreover, ROS content was increased and SOD activity was reduced, while the NF-κB presentation was increased. The above-mentioned changes could be reversed in IR set, DEX set and miR-106a-NPs set. The action was more notable in the DEX and miR-106a-NPs sets. Finally, the proliferation in hippocampus neuron in hypoxia-reoxygenation injury could be prompted and apoptosis could be restrained by DEX and miR-106a-NPs. The secretion of inflammatory factors could be restrained through restraining the inflammatory pathway and oxidative stress. The energy metabolism could therefore be improved effectively and recovery of nerve cells in HBI could be improved.

Serum glial fibrillary acidic protein and S100 calcium-binding protein B correlates cerebral vessel reactivity following carotid artery stenting.

Using detection markers in serum has the advantages of simplicity, repeatability and the capability. This study combined the use of serum glial fibrillary acidic protein (GFAP) and S100B protein (S100B) with imaging tools to confirm the role of serum biomarkers in evaluating the cerebral vessel reactivity after carotid artery stenting (CAS). After CAS, the serum concentrations of GFAP and S100B increased to the peak at 24 h after operation, and then gradually decreased. The mean flow velocity (MFV) (pre-operation, post-operation, 30 days follow-up: 47.65 ± 17.24 cm/s, 62.37 ± 18.25 cm/s, 70.29 ± 16.89 cm/s; P < 0.05) and pulsatility index (PI) (pre-operation, post-operation, 30 days follow-up: 0.78 ± 0.21, 0.98 ± 0.19, 1.02 ± 0.20; P < 0.05) increased significantly in the ipsilateral middle cerebral artery after CAS. At the 30-day follow-up, the cerebrovascular reserve (CVR) (post-operation, 30 days follow-up: 27.47 ± 12.13 cm/s, 31.92 ± 10.94 cm/s; P < 0.05) improved significantly. In patients with different degrees of stenosis, the more severe the stenosis in the carotid artery, the more obvious the improvement of CVR at the 30 days of follow-up (CVR changes: 11.08 ± 7.95 cm/s, Kendall's tau-b = 0.645, P < 0.001). And the serum concentrations of GFAP (r = - 0.629, P < 0.0001) and S100B (r = - 0.604, P < 0.0001) correlated negatively with CVR at 30 days after CAS. Therefore, we recommend using the biomarkers GFAP and S100B associated with imaging tools such as transcranial Doppler (TCD) and Magnetic resonance imaging (MRI) to evaluate the cerebral vessel reactivity following CAS.

Melatonin Receptor Agonist Ramelteon Suppresses LPS-Induced Neuroinflammation in Astrocytes.

Astrocytes-mediated neuroinflammation has been involved in the process of several neurodegenerative diseases. Ramelteon is a novel agonist of melatonin receptors and licensed for the management of insomnia. In this study, our results demonstrate that Ramelteon ameliorated lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes. First, we found that the optimized incubation concentrations of Ramelteon applied in the present study were 50 and 100 nM. Second, treatment with Ramelteon reduced expressions of IL-6, TNF-α, and IL-1ß. Additionally, Ramelteon prevented an LPS-induced increase in the expressions of iNOS, COX-2, NO, and PGE2. Importantly, we found that Ramelteon reduced the expression of GFAP. Mechanistically, we found that Ramelteon inhibited the TLR4/IκBα/NF-κB p65 axis. Notably, the protective effects of Ramelteon were verified in an in vivo rodent model. Based on these findings, we concluded that Ramelteon might prevent LPS-induced damage in astrocytes.

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke.

BACKGROUND: Mental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients. METHODS: This study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems. RESULTS: The high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)]. CONCLUSIONS: These findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS.

NSE, S100B and MMP9 Expression Following Reperfusion after Carotid Artery Stenting.

OBJECTIVE: Previous studies have shown that the neuron-specific- enolase (NSE), S100B protein (S100B) and matrix metalloproteinase-9 (MMP9) are specific markers for studying cerebral injury. This study was aimed to demonstrate these biomarkers for their correlation with reperfusion after carotid artery stenting (CAS). METHODS: In this study, a total of 44 patients who were diagnosed unilateral carotid artery stenosis by digital subtraction angiography (DSA) and underwent CAS, were selected as the operation groups. The patients' blood samples were collected at three different time points: T1, prior to operation; T2, next morning after operation (24 hours); T3, three days after operation (72 hours); All of the patients with the operation received computed tomography perfusion (CTP) at T1 and T3. The second group of 12 patients, who were excluded for carotid artery stenosis by DSA, were assigned to be the control group; Blood samples of these patients were collected at T1. The concentrations of NSE, S100B and MMP9 in serum from patients of both groups were detected by ELISA. RESULTS: All of the operations were implanted in stents successfully without complications. (1) After CAS, rCBF increased while rMTT and rTTP decreased. (2) The concentrations of NSE, S100B and MMP9 in the serum decreased gradually (T1>T2>T3). There was no significant difference between the control group and the operation group at T1 (P>0.05) on their concentrations of NSE, S100B and MMP9 in the serum. When compared among the operation groups, the concentrations of NSE, S100B and MMP9 in the serum at T1 and T3 showed significant difference (P<0.05). (3) Correlation analysis among the operation groups indicated that NSE, S100B, MMP9 and rCBF were positively correlated before operation (r = 0.69, 0.58 and 0.72, respectively, P < 0.05), as well as after operation (r = 0.75, 0.65 and 0.60, respectively, P < 0.05). CONCLUSION: We concluded that the concentrations of NSE, S100B and MMP9 in serum decreased with the improvement of cerebral reperfusion after CAS. NSE, S100B and MMP9 can be used as laboratory biochemical markers to evaluate the improvement of reperfusion after CAS. The results very well complement the imaging methods, such as CTP.

Efficacy and safety of NAD+ ADP-ribosyltransferase 1 agonist versus Donepezil in elderly Chinese patients with Alzheimer disease: A novel target for effective therapy.

This pilot study designed to evaluate the efficacy and safety of NAD+ ADP-ribosyl transferase 1 (NART) agonist in comparison with Donepezil (DNP) in elderly Chinese patients with Alzheimer disease (AD). In the present clinical trial, Chinese elderly patients aged >65 years with a confirmed diagnosis of AD were enrolled. The patients received NART agonist (test, DAG-structured PKC blockers (GF109203X)) or DNP 10mg daily (reference) for 6 months. The efficacy and safety data were collected from 120 patients (60 patients in each group) every 3 weeks until 6 months. The primary endpoints were to assess the change in cognitive score from baseline in both the treatment group. The result of the present study showed that the patients treated with DNP and NART agonist have similar efficacy and safety profile. Considering the clinical benefit, improvement in sign and symptoms of was numerically greater in DNP-treated patients as compared to NART agonist. However, a statistical difference in terms of clinical benefit was similar between both the treatment groups. Overall, both the study drugs were found comparable in relieving the symptoms of AD. This indicates that NART is a potential target for the treatment of AD in China. The results of the present study may help to design a large clinical trial to evaluate the efficacy and safety of NART agonist in comparison with DNP in AD patients.

Inflammatory cytokines and cells are potential markers for patients with cerebral apoplexy in intensive care unit.

Cerebral apoplexy is a disease caused by obstruction of the blood circulation in the brain. Evidence has indicated that inflammatory cytokines are implicated in ischaemic cerebral apoplexy and are regarded as a general cardiovascular risk factor, which may be a possible immediate trigger, a component of the response to tissue injury and a therapeutic target. The present study investigated changes of inflammatory cytokines and cells in patients with cerebral apoplexy at the intensive care unit (ICU). The plasma concentrations of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-1ß and IL-17A were evaluated using ELISA. Changes in the plasma concentrations of inflammatory cells were detected by using flow cytometry. The results indicated that serum levels of TNF-α, IL-4, IL-8, IL-1ß and IL-17A were upregulated in patients with cerebral apoplexy compared with those in healthy individuals, while those of IL-6 and IL-10 were downregulated. Furthermore, it was demonstrated that the plasma concentration of lymphocytes, granulocytes and mononuclear cells was decreased in patients with cerebral apoplexy in the ICU compared with that in healthy individuals. Of note, humoral as well as cellular inflammatory cytokines were evidently increased in patients with cerebral apoplexy in ICU. In conclusion, the present study provided evidence that inflammatory cytokines and inflammatory cells are upregulated, while anti-inflammatory cytokines are downregulated in patients with cerebral apoplexy in an ICU setting. These results suggest that anti-inflammatory interventions may be beneficial either in the prevention or acute treatment of patients with cerebral apoplexy.

Resveratrol Inhibits Diabetic-Induced Müller Cells Apoptosis through MicroRNA-29b/Specificity Protein 1 Pathway.

The aim of this study was to evaluate the anti-apoptosis effects of resveratrol (RSV) on diabetic rats retinal Müller cells in vivo and in vitro and to further investigate the roles of microRNA-29b (miR-29b)/specificity protein 1 (SP1) in the anti-apoptosis mechanism of RSV. Retina was obtained from normal and diabetic rats with or without RSV (5 and 10 mg/kg/day) treatments at 1-7 months. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and Annexin V/PI staining were used to detect apoptosis. Immunofluorescence was used to assess distribution of SP1 in retina. MiR-29b and SP1 messenger RNA (mRNA) expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). SP1, Bax, and bcl-2 protein expression was evaluated by western blotting. Caspase-3 activity was detected by assay kit. Our study showed that the TUNEL-positive cells were mainly localized in the inner nuclear layer (INL) of retina and RSV administration effectively suppressed streptozotocin (STZ)-induced apoptosis of retinal cells in INL in vivo (P < 0.001). Our study also showed that RSV administration effectively suppressed high glucose (HG)-induced retinal Müller cells' apoptosis in vitro (P < 0.001). Furthermore, our study revealed that the diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro (P < 0.05). The anti-apoptosis effect and downregulated SP1 expression effect of RSV was prevented by miR-29b inhibitor (P < 0.05). MiR-29b mimic increased the above-mentioned effects of RSV (P < 0.001). These findings indicate that RSV is a potential therapeutic option for diabetic retinopathy (DR) and that miR-29b/SP1 pathway play roles in the anti-apoptosis mechanism of RSV.

Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina.

This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy.

Redox factor 1 inhibits the apoptosis process after intracerebral hemorrhage.

OBJECTIVE: To determine the role of redox factor 1 (Ref-1) in the apoptotic process in perihematoma brain tissue from intracerebral hemorrhage (ICH) patients. METHODS: Thirty ICH patients were selected, and normal brain tissue, inevitably lost during surgery, was used as the control group, while the brain tissue from 1 cm around the hematoma was used as the experimental group. Experimental tissues were further divided according to the time from syndrome onset to the time of operation as follows: <6 hours (n = 6); 6-12 hours (n = 7); 12-24 hours (n = 5); 24-72 hours (n = 6); and >72 hours (n = 6). Apoptotic cells were observed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) reaction. Protein and mRNA expression of Ref-1 and Bax were determined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively. RESULTS: Immunohistochemistry indicated that Ref-1 expression was the maximal in control tissue, while it slowly declined to a nadir between 12 and 72 hours in the experimental tissue. Bax expression was the lowest in the control tissue, and gradually increased from 12 to 72 hours in the experimental tissue. RT-PCR data showed that patterns of Ref-1 and Bax expression similar to the immunohistochemistry results. Correlation analysis demonstrated a negative correlation among Ref-1, apoptosis, and Bax. CONCLUSION: Ref-1 may play an important role in protecting brain cells and may be able to inhibit apoptosis following ICH.