Impact of White Matter Hyperintensity and Age on Gait Parameters in Patients With Cerebral Small Vessel Disease.

OBJECTIVES: This study aimed to investigate the effect of white matter hyperintensity (WMH), a common cerebral small vessel disease (CSVD) imaging marker, and age on gait parameters in middle-aged and geriatric populations. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1076 participants (62.9% female; age 61.0 ± 9.3 years), who visited the neurology clinic or obtained a physical check-up from the Affiliated Hospital of Guizhou Medical University. In total, 883 patients with WMH and 193 healthy controls were included in this study. METHODS: The Fazekas scores of patients with CSVD were used to assess the burden of WMH. Based on the Fazekas scores, all participants were divided into 4 groups: 553 patients with Fazekas I, 257 patients with Fazekas II, 73 patients with Fazekas III, and 193 controls. Gait parameters, including step speed, frequency, length, width, stance time, and swing time, were quantitatively assessed using a vision-based artificial intelligence gait analyzer (SAIL system). The relationships among the Fazekas scores, age, and gait parameters were analyzed. RESULTS: Step speed, step length, step width, stance time, and swing time were significantly different among the 4 groups. Furthermore, Fazekas scores and age were both associated with gait parameters, including step speed, step length, stance time, and swing time. The Fazekas scores were associated with step width, whereas age was not. Age was associated with step frequency, whereas Fazekas scores were not. CONCLUSIONS AND IMPLICATIONS: Fazekas score and age are useful for evaluating gait parameters in patients with CSVD. Emerging WMH (such as Fazekas Ⅰ) could be a clinical warning sign of gait disturbance in a geriatric population.

Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-ß axis.

Currently, the reported source of extracellular vesicles (EVs) for the treatment of ischemic stroke（IS）is limited to mammals. Moreover, these EVs are restricted to clinical translation by the high cost of cell culture. In this respect, Lactobacillus plantarum culture is advantaged by low cost and high yield. However, it is poorly understood whether Lactobacillus plantarum-derived EVs (LEVs) are applicable for the treatment of IS. Here, our results demonstrated that LEVs reduced apoptosis in ischemic neuron both in vivo and in vitro. As revealed by high-throughput sequencing, miR-101a-3p expression was significantly elevated by LEV treatment in OGD/R-induced neurons, as confirmed in the tMCAO mice treated with LEVs. Mechanistically, c-Fos was directly targeted by miR-101a-3p. In addition, c-Fos determined ischemia-induced neuron apoptosis in vivo and in vitro through the TGF-ß1 pathway, miR-101a-3p inhibition aggravated ischemia-induced neuron apoptosis in vitro and in vivo, and miR-101a-3p overexpression produced the opposite results. Hsa-miR-101-3p was downregulated in the plasma of patients with IS but upregulated in the patients with neurological recovery after rt-PA intravenous thrombolysis. In conclusion, Our results demonstrated for the first time that LEVs might inhibit neuron apoptosis via the miR-101a-3p/c-Fos/TGF-ß axis, and has-miR-101-3p is a potential marker of neurological recovery in IS patients.

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats.

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.

Risk factors of cerebral microbleeds in young and middle-aged patients with hypertension.

Objective This study aimed to investigate the incidence and related risk factors of cerebral microbleeds (CMBs) in young and middle-aged patients with hypertension. Methods The study included 232 young and middle-aged (18-59 years-old) patients with hypertension from September 2014 to December 2016 in the Department of Neurology, Affiliated Hospital of Guizhou Medical University, China. The data were recorded which included demographics, vascular risk factors, medication history, and imaging data of patients. CMBs were evaluated based on the microbleeds anatomical rating scale. Results Of the enrolled participants, 115 were CMB positive, accounting for 49.6%. CMBs were more prone to occur in deep regions than in others (39.13%). Multiple cerebral microbleeds were associated with white matter hyperintensities(WMH), dyslipidemia, hyperhomocysteine, and uric acid. Moreover, WMH, dyslipidemia, ever smoker, antiplatelets use, and hyperhomocysteine were found to be risk factors for deep or infratentorial CMBs in young and middle-aged patients with hypertension. However, the lobar CMBs only had an independent correlation with dyslipidemia in these participants. Conclusions The incidence of CMBs in patients with hypertension was relatively high. It mostly occurred in a deep or infratentorial area with more vascular-associated risk factors. However, in patients with lobar CMBs, factors associated with lipid metabolism, such as amyloid deposition and unidentified genotype variation, may be crucial. Screening and regular follow-ups of CMBs by Susceptibility Weighted Imaging and active prevention in young and middle-aged patients with hypertension have clinical significance for timely understanding and predicting the occurrence and development of related cerebrovascular disease events.

Association Between the Single Nucleotide Polymorphism and the Level of Aquaporin-4 Protein Expression in Han and Minority Chinese with Inflammatory Demyelinating Diseases of the Central Nervous System.

The purpose of this study was to determine whether or not aquaporin-4 (AQP4) gene mutations are related to the pathogenesis of inflammatory demyelinating diseases in the central nervous system. Polymorphisms of AQP4 exons 1-5 were determined by sequencing DNA from 67 patients with central nervous system inflammatory demyelinating diseases, including neuromyelitis optica (NMO), multiple sclerosis, recurrent or simultaneous bilateral optic neuritis, and longitudinally extensive transverse myelitis. A plasmid with the identified new missense mutation was constructed, and human embryonic kidney cells (HEK293A) were transfected with either the pEGFP-N1-AQP4-M23 vector (bearing the identified mutated cDNA sequence) or with the plasmid bearing the wild-type AQP4 gene sequence. AQP4 protein expression was analyzed in both experimental groups using Western Blot analysis following protein extraction from transfected cells. A synonymous mutation (rs1839318) was detected on exon 3, and an additional synonymous mutation was detected on the exon 2-2 (rs72557968). Most importantly, a new missense mutation was detected on exon 2-1. According to Western blot analysis, the mutated cDNA sequence yielded increased AQP4 protein expression in comparison with the wild-type cDNA sequence (P < 0.05). AQP4 gene mutations are uncommon, occurring in only 3 out of 67 patients. Although it is possible that the mutations contributed to an increased risk of inflammatory central nervous system disease in these individuals, it is unlikely that mutations are a significant contributor to most patients with NMO spectrum disorders in China.