Sex Differences in the Association Between LDL/HDL with Cognitive Decline in Older Adults: National Health and Nutrition Examination Survey.

Background: Lipids have a significant impact on the development and functioning of the nervous system, but the sex differences between the association of LDL/HDL, which reflects lipid metabolic status, and cognitive impairment remains unclear. Objective: We aimed to determine if there were sex differences between the association of LDL/HDL and cognitive function in US older adults. Methods: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014 cycles. The main outcome was poor cognitive performance defined by the Digit Symbol Substitution Test (DSST) <  34 based on published literature. Results: A total of 1,225 participants were included in the study, with a cognitive impairment incidence of 25.6% (314/1,225). Multivariate regression models demonstrated a significant association between cognitive decline and each 1-unit increase in LDL/HDL, after adjusting for all covariates (adjusted odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.11-1.67). Furthermore, subgroup analysis revealed an interaction between LDL/HDL and cognitive impairment in sex subgroups. Conclusions: LDL/HDL was associated with cognitive impairment in the US older adult population in adjusted models, although the significance of this association was not observed in females.

Corrigendum to "Long-term L-3-n-butylphthalide pretreatment attenuates ischemic brain injury in mice with permanent distal middle cerebral artery occlusion through the Nrf2 pathway" [Heliyon 8 (7), (July 2022), Article e09909].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09909.].

Long-term L-3-n-butylphthalide pretreatment attenuates ischemic brain injury in mice with permanent distal middle cerebral artery occlusion through the Nrf2 pathway.

L-3-n-butylphthalide (NBP), which is used for treatment of mild and moderate acute ischemic stroke, exerts its effects by modulating the Nrf2 pathway. However, it has not been established whether NBP exerts its preventive effects in high-risk ischemic stroke patients through the Nrf2 pathway. We investigated whether NBP exerts its preventive effects through the Nrf2 pathway in long-term NBP pretreated dMCAO mice models. Nrf2+/+ wild-type and Nrf2-/- knockout mice were randomized into the vehicle group (equal volume vegetable oil), NBP-low-dose group (20 mg/kg) and NBP-high-dose group (60 mg/kg). The drug was administered once daily by gavage for a month. Then, a permanent distal middle cerebral artery occlusion model (dMCAO) was established after pretreatment with NBP. Neurological deficits, cerebral infarct volumes, brain water contents, activities of SOD, GSH-Px and MDA levels were determined. Further, axonal injury and demyelination, expression levels of Nrf2, HO-1 and NQO1 in ischemic brains were determined. Long-term NBP pretreatment significantly improved neurological functions, reduced cerebral infarction volumes, reduced brain water contents, increased SOD, GSH-Px activities, decreased MDA contents, reduced neurological injuries, axonal damage as well as demyelination, while increasing Nrf2, HO-1 and NQO1 mRNA as well as protein expressions in dMCAO mice models.

Susceptibility-diffusion mismatch correlated with leptomeningeal collateralization in large vessel occlusion stroke.

OBJECTIVE: To investigate the relationship between asymmetric prominent hypointense vessels (prominent vessel sign, PVS) on susceptibility-weighted imaging (SWI) and leptomeningeal collateralization in patients with acute ischemic stroke due to large vessel occlusion. METHODS: We retrospectively enrolled patients with M1 segment occlusion of the middle cerebral artery who underwent emergency magnetic resonance imaging and digital subtraction angiography within 24 hours from stroke onset. The extent of PVS on SWI was assessed using the Alberta Stroke Program Early CT Score (ASPECTS). Leptomeningeal collateralization on digital subtraction angiography images was assessed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. Spearman's rank correlation test was performed to explore the correlation of ASITN/SIR scores with SWI-ASPECTS and SWI-diffusion-weighted imaging (DWI) mismatch scores. RESULTS: Thirty-five patients were enrolled. There was no significant correlation between SWI-ASPECTS and ASITN/SIR scores. However, SWI-DWI mismatch scores were positively correlated with ASITN/SIR scores. CONCLUSION: The range of PVS on SWI did not closely reflect the collateral status, while the range of SWI-DWI mismatch was significantly correlated with the leptomeningeal collateralization. In patients with acute anterior circulation stroke due to large vessel occlusion, larger SWI-DWI mismatch was associated with better leptomeningeal collaterals.

Factors associated with prominent vessel sign on susceptibility-weighted imaging in acute ischemic stroke.

The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5-53.3), large vessel occlusion (OR 123.3; 95% CI 33.7-451.5), and cardioembolism (OR 5.6; 95% CI 2.1-15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.

P2Y12 receptor-mediated microglia activation involved in delayed encephalopathy after acute carbon monoxide poisoning.

To investigate the role of P2Y12 receptor-mediated microglia activation in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), we used static inhalation carbon monoxide to build DEACMP rat model. DEACMP rats were randomly assigned into DEACMP group and intervention group. A control goup was also set. The rats in intervention group received intraperitoneal injection of 100uM suramin (a P2Y12 receptor antagonist). In control group, the escape latency, level of microglia activation and ATP content were similar between different time points. In both DEACMP group and intervention group, the escape latency, level of microglia activation and ATP content were significanlty increased at 21th and 28th day. The hippocampal cells in DEACMP group and intervention group were severely and moderately, respectively, damaged at 21th and 28th day. Meanwhile, compared to control group, both DEACMP group and intervention group had significanlty longer escape latency, higher level of microglia activation and ATP content at 21th and 28th day. Compared to DEACMP group, the intervention group had significantly shorter escape latency and lower level of microglia activation at 21th and 28th day. These results suggested that the microglia activation regulated by ATP through P2Y12 receptor pathway might be closely related to the development of DEACMP.

The relation between plasma miR-126 levels and cerebral collateral circulation in patients with intracranial arterial stenosis.

OBJECTIVE: This study aimed to investigate the correlation between the circulating miR-126 regulation pathway and the cerebral collateral circulation (CCC), and to test whether miR-126 could serve as a potential biomarker for CCC formation in patients with intracranial arterial stenosis or occlusion. MATERIAL AND METHODS: This single-centre cross-sectional study enrolled patients who underwent cerebral angiography with severe stenosis (≥70%) or occlusion in at least one major intracranial artery. Collateral degree was graded according to the ASITN/SIR classification. The patients were divided into a good CCC group (grade 3-4) or a poor CCC group (grade 0-2). We investigated the plasma levels of miR-126, VEGF, Spred-1 and PIK3R2 by using qRT-PCR, ELISA and Western blot methods, respectively. In addition, we assessed the correlations of plasma miR-126 with VEGF, Spred-1, PIK3R2 and ASITN/SIR grade using the Spearman correlation test and investigated its predictive power for CCC status by using the receiver operating characteristic curve. RESULTS: A total of 68 patients were enrolled (44 with good CCC and 24 with poor CCC). Data showed that plasma miR-126 and VEGF were significantly higher in the good CCC group than in the poor CCC group. Plasma Spred-1 and PIK3R2 level were lower in the good CCC group than in the poor CCC group. In addition, miR-126 and VEGF were positively correlated with ASITN/SIR (miR-126: R = 0.595, P < 0.01; VEGF: R = 0.595, P < 0.01), whereas Spred-1 and PIK3R2 were negatively correlated with ASITN/SIR (Spred-1: R = -0.817, P < 0.01; PIK3R2: R = -0.513, P=0.01). However, the area under the curve of miR-126 level for CCC status was only 0.328 (95% CI: 0.158-0.498; p = 0.067). CONCLUSIONS: Plasma miR-126 level may be related to better CCC formation, one of the mechanisms that may be explained by upregulation of VEGF and reduction of Spred-1 and PIK3R2 protein expression. However, miR-126 might not be an independent predictor for CCC, given its low predictive value.

Interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in large vessel occlusion stroke.

OBJECTIVE: To investigate the interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in patients with acute ischemic stroke due to large vessel occlusion. METHODS: In this prospective study, consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission, including diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and time-of-flight magnetic resonance angiography (TOF-MRA). Patients with large vessel occlusion within the anterior circulation were recruited. Follow-up MRI was performed within 24 h after recanalization therapy (intravenous thrombolysis, endovascular therapy, or both). Multivariable logistic regression analysis was performed to estimate the interaction between SWI-DWI mismatch score and recanalization status on clinical outcome. RESULTS: A total of 90 patients were enrolled. A multiplicative interaction between SWI-DWI mismatch score and recanalization status on clinical outcome was observed (P=0.037). The interaction term "SWI-DWI mismatch score × successful recanalization" was significantly associated with favorable outcome (modified Rankin Scale score of 0-2 at 90 days; adjusted odds ratio [aOR], 2.162; 95% confidence interval [CI], 1.046-4.468). Stratified analysis showed that the likelihood of favorable outcome increased with the increase of SWI-DWI mismatch score in the successful recanalization group (OR, 2.140; 95% CI, 1.376-3.326), while there was no significant relationship between SWI-DWI mismatch score and clinical outcome in the unsuccessful recanalization group (OR, 1.212; 95% CI, 0.933-1.574). CONCLUSIONS: The effects of SWI-DWI mismatch and recanalization status on clinical outcome were realized through their interaction. In anterior circulation stroke due to large vessel occlusion, patients with both high SWI-DWI mismatch scores and successful recanalization were more likely to achieve a favorable outcome, while patients with unsuccessful recanalization, or with successful recanalization but low SWI-DWI mismatch scores, were less likely to have a good prognosis.

Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH).

AIM: To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk. METHODS: We conducted whole-exome sequencing (WES) in a cohort of 196 individuals, including 94 SAH patients and 94 controls, as well as 8 samples that belong to two pedigrees. Systematically examination for rare variations (through direct genotyping) and common variations (through genotyping and imputation) for SAHs were performed in this study. RESULTS: A total of 16,029 single-nucleotide polymorphisms (SNPs) and 108,999 short indels were detected in all samples, and among them, 30 SNPs distributed on 17 genes presented a strong association signal with SAH. Two novel pathogenic gene variants were identified as associated risk loci, including mutation in TPO and PALD1. The statistical analysis for rare, damaging variations in SAHs identified several susceptibility genes which were involved in degradation of the extracellular matrix and transcription factor signal pathways. And 25 putative pathogenic genes for SAH were also identified basic on functional interaction network analysis with the published SAH-associated genes. Additionally, pedigree analysis revealed autosomal dominant inheritance of pathogenic genes. CONCLUSION: Systematical analysis revealed a key role for rare variations in SAH risk and discovered SNPs in new complex loci. Our study expanded the list of candidate genes associated with SAH risk, and will facilitate the investigation of disease-related mechanisms and potential clinical therapies.

Combined application of dexamethasone and hyperbaric oxygen therapy yields better efficacy for patients with delayed encephalopathy after acute carbon monoxide poisoning.

BACKGROUND: Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) commonly occurs after recovering from acute CO poisoning. This study was performed to assess the efficacy of the combined application of dexamethasone and hyperbaric oxygen (HBO) therapy in patients with DEACMP. PATIENTS AND METHODS: A total of 120 patients with DEACMP were recruited and randomly assigned into the experimental group (receiving dexamethasone 5 mg/day or 10 mg/day plus HBO therapy) and control group (HBO therapy as monotherapy). Meanwhile, the conventional treatments were provided for all the patients. We used the Mini-Mental State Examination (MMSE) scale to assess the cognitive function, the National Institutes of Health Stroke Scale (NIHSS) to assess the neurological function and the remission rate (RR) to assess the clinical efficacy. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was also measured. RESULTS: After 4 weeks of treatment, compared to the control group, the experimental group had a significantly higher remission rate (P=0.032), a significantly higher average MMSE score (P=0.037) and a significantly lower average NIHSS score (P=0.002). Meanwhile, there was a trend toward better improvement with dexamethasone 10 mg/day, and the level of MBP in the CSF of patients was significantly lower in the experimental group than in the control group (P<0.0001). The addition of dexamethasone did not significantly increase the incidence of adverse events. CONCLUSION: These results indicate that the combined application of dexamethasone and HBO therapy could yield better efficacy for patients with DEACMP and should be viewed as a potential new therapy.

Efficacy of N-Butylphthalide and Hyperbaric Oxygen Therapy on Cognitive Dysfunction in Patients with Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

BACKGROUND Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is one of the most serious complications after CO poisoning. This study was conducted to explore the efficacy of the combined application of N-Butylphthalide and hyperbaric oxygenation therapy (HBO) on cognitive dysfunction in patients with DEACMP. MATERIAL AND METHODS A total of 184 patients with DEACMP were randomly assigned to either receive HBO or N-Butylphthalide and HBO. Meanwhile, all patients received conventional treatment. The total remission rate (RR) was used to assess the clinical efficacy. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function, and the National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological function. RESULTS Finally, there were 90 and 94 patients in the control and experimental groups, respectively. After eight weeks of treatment, the total RR in the experimental group (47.9%) was significantly higher than that in the control group (33.3%). Compared to the control group, significantly more patients in the experimental group had MMSE scores of 24-30. The lower NIHSS score in the experimental group showed that N-Butylphthalide had the effect of preservation and restoration of neurological function. No obvious drug toxicity or liver and kidney dysfunction was observed, and there was no significant change in the level of blood glucose and blood lipids. CONCLUSIONS These results indicated that the combined application of N-Butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DEACMP and have great clinical efficacy, which should be further studied.

Correlation between aortic/carotid atherosclerotic plaques and cerebral infarction.

The aim of this study was to investigate the correlation between aortic/carotid atherosclerotic plaques and cerebral infarction. We examined 116 cases of cerebral infarction using transcranial Doppler ultrasound in order to exclude cerebrovascular stenosis. Transesophageal echocardiography and color Doppler ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116 cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%). The difference in the incidence of various types of infarction between APP severity levels was significant (P<0.01). Of the 116 cases, 64 had CAPs (55.2%), including 46 with unstable plaque (39.7%). The difference in the incidence of various types of infarction between CAP stability levels was significant (P<0.01). The results indicate that moderate/severe AAP and unstable CAP are significant causes of embolic infarction without stenosis in the internal carotid arteries.

Role of Neurotrophin 3 in spinal neuroplasticity in rats subjected to cord transection.

That neuroplasticity occurs in mammalian spinal cord is well known, though the underlying mechanism still awaits elucidation. This study evaluated the role of endogenous Neurotrophin-3 (NT-3) in the spinal neuroplasticity. Following cord transection at the junction between T9 and T10, the hindlimb locomotor functions of rats showed gradual but significant improvement from 7 to 28 days post-operation. Corresponding to this was a significant increase in the level of NT-3 in the cord segments caudal to injury site. Significantly, after NT-3-antibody administration, the spinal transected rats displayed poor hindlimb locomotor functions and a decrease in the number of neurons in spinal laminae VIII-IX. Whether NT-3-antibody was administered, corticospinal tract regeneration and somatosensory evoked potentials could not be detected. Our findings suggested that endogenous NT-3 could play an important role in spinal plasticity in adult spinal cords subjected to transection, possibly through a regulation of neuronal activity in the local circuitry.

Effects of electro-acupuncture on IGF-I expression in spared dorsal root ganglia and associated spinal dorsal horn in cats subjected to adjacent dorsal root ganglionectomies.

The effects of electro-acupuncture (EA) on insulin-like growth factor-I (IGF-I) expression in the spared dorsal root ganglia (DRG) and associated spinal dorsal horns were explored in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG, sparing the L(6) DRG. Immunohistochemistry revealed the presence of IGF-I immunoreactive products in the L(6) DRG neurons and some neurons and glial cells in the spinal cord. Western blot demonstrated that the level of IGF-I was significantly up-regulated both in the spared DRG and the dorsal horns of L(3) and L(6) cord segments at both 7 and 14 days post operation following EA. The present findings demonstrated the association between neuroplasticity and IGF-I expression, suggesting the possible role of IGF-I in EA promoted spinal cord plasticity.

Effects of engrafted neural stem cells derived from GFP transgenic mice in Parkinson's diseases rats.

This study evaluated the therapeutic effect of neural stem cells (NSCs) transplanted into Parkinson's disease (PD) rats. NSCs were identified in vitro, then engrafted into the striatum of the PD rats. The rotational behavior was evaluated 1, 2, 4 and 6 weeks. A significant rotational behavior improvement was observed in PD rats subjected to cell transplantation. Transplanted NSCs not only express Nerve growth factor and Neurotrophin-3 in vitro, but also survive and partly differentiate into tyrosine hydroxylase (TH) positive cells in vivo. The results show that NSCs could be effective for PD treatment and the mechanisms might involve the neurotrophin expression and the neural differentiation.