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1.
Neuron ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38653248

ABSTRACT

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.

2.
ACS Chem Neurosci ; 15(2): 382-393, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38155530

ABSTRACT

Major facilitator superfamily domain-containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine cotransporter that plays an important role in maintaining the integrity of the blood-brain barrier and neurological function. Abnormal degradation of Mfsd2a often leads to dysfunction of the blood-brain barrier, while upregulation of Mfsd2a can retrieve neurological damage. It has been reported that Mfsd2a can be specifically recognized and ubiquitinated by neural precursor cell-expressed developmentally downregulated gene 4 type 2 (NEDD4-2) ubiquitin ligase and finally degraded through the proteasome pathway. However, the structural basis for the specific binding of Mfsd2a to NEDD4-2 is unclear. In this work, we combined deep learning and molecular dynamics simulations to obtain a Mfsd2a structure with high quality and a stable Mfsd2a/NEDD4-2-WW3 interaction model. Moreover, molecular mechanics generalized Born surface area (MM-GBSA) methods coupled with per-residue energy decomposition studies were carried out to analyze the key residues that dominate the binding interaction. Based on these results, we designed three peptides containing the key residues by truncating the Mfsd2a sequences. One of them was found to significantly inhibit Mfsd2a ubiquitination, which was further validated in an oxygen-glucose deprivation (OGD) model in a human microvascular endothelial cell line. This work provides some new insights into the understanding of Mfsd2a and NEDD4-2 interaction and might promote further development of drugs targeting Mfsd2a ubiquitination.


Subject(s)
Blood-Brain Barrier , Molecular Dynamics Simulation , Humans , Biological Transport , Blood-Brain Barrier/metabolism , Cell Line , Ubiquitination
3.
Front Pharmacol ; 14: 1091616, 2023.
Article in English | MEDLINE | ID: mdl-36814490

ABSTRACT

Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.

5.
Front Neurosci ; 16: 639656, 2022.
Article in English | MEDLINE | ID: mdl-35495024

ABSTRACT

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.

6.
Trends Endocrinol Metab ; 33(6): 390-400, 2022 06.
Article in English | MEDLINE | ID: mdl-35396164

ABSTRACT

Reactive astrocytes undergo morphological, molecular, metabolic, and functional remodeling in response to central nervous system (CNS) damage. However, we still know very little about how the metabolic switching of astrocytes influences, or is influenced by, reactive astrocytes in response to neurological diseases. In this review, we initially cover a brief introduction into reactive astrocyte function under pathological conditions. Subsequently, we summarize the emerging roles of glucose and lipid metabolism in reactive astrocytes in the context of CNS injury to provide a new insight into metabolic mechanisms of reactive astrocyte-mediated neuroprotection or damage. Finally, we propose that deciphering the mechanistic link between astrocyte heterogeneity metabolism and improved methods is an emerging frontier for the therapeutic investigation of CNS injury and disease.


Subject(s)
Astrocytes , Central Nervous System , Astrocytes/metabolism , Astrocytes/pathology , Central Nervous System/metabolism , Glucose/metabolism , Humans
7.
Cell Mol Neurobiol ; 42(6): 1897-1908, 2022 Aug.
Article in English | MEDLINE | ID: mdl-33712886

ABSTRACT

Neurons in the penumbra (the area surrounding ischemic tissue that consists of still viable tissue but with reduced blood flow and oxygen transport) may be rescued following stroke if adequate perfusion is restored in time. It has been speculated that post-stroke angiogenesis in the penumbra can reduce damage caused by ischemia. However, the mechanism for neovasculature formation in the brain remains unclear and vascular-targeted therapies for brain ischemia remain suboptimal. Here, we show that VEGFR1 was highly upregulated in pericytes after stroke. Knockdown of VEGFR1 in pericytes led to increased infarct area and compromised post-ischemia vessel formation. Furthermore, in vitro studies confirmed a critical role for pericyte-derived VEGFR1 in both endothelial tube formation and pericyte migration. Interestingly, our results show that pericyte-derived VEGFR1 has opposite effects on Akt activity in endothelial cells and pericytes. Collectively, these results indicate that pericyte-specific expression of VEGFR1 modulates ischemia-induced vessel formation and vascular integrity in the brain.


Subject(s)
Ischemic Stroke , Stroke , Cerebrovascular Circulation/physiology , Endothelial Cells/metabolism , Humans , Ischemia/metabolism , Perfusion , Pericytes , Stroke/metabolism
8.
Neurology ; 97(22): e2152-e2163, 2021 11 30.
Article in English | MEDLINE | ID: mdl-34649885

ABSTRACT

OBJECTIVE: To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice. METHODS: Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes included function independence (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable). RESULTS: Among 639 eligible patients, the median age was 64 years, and median OPT was 328 minutes (interquartile range 220-490). Treatment within 4-8 hours and 8-12 hours was associated with lower rates of favorable outcome (adjusted odds ratio, 0.63 [95% confidence interval (CI), 0.40-0.98] and 0.47 [95% CI, 0.23-0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome (p nonlinearity = 0.028) and functional independence (p nonlinearity = 0.025), with significant benefit loss throughout the first 9 hours, but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then leveled off (p nonlinearity = 0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant. CONCLUSION: Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier EVT is associated with better outcomes.


Subject(s)
Arterial Occlusive Diseases , Endovascular Procedures , Ischemic Stroke , Stroke , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/surgery , Basilar Artery/diagnostic imaging , Basilar Artery/surgery , Humans , Middle Aged , Odds Ratio , Stroke/complications , Stroke/surgery , Treatment Outcome
9.
Front Neurol ; 12: 593914, 2021.
Article in English | MEDLINE | ID: mdl-34177752

ABSTRACT

Objective: Mechanical thrombectomy (MT) has been an effective first-line therapeutic strategy for ischemic stroke. With impairment characteristics separating it from anterior circulation stroke, we aimed to explore prognostic structural neural markers for basilar artery occlusion (BAO) after MT. Methods: Fifty-four BAO patients with multi-modal magnetic resonance imaging at admission from the multicenter real-world designed BASILAR research were enrolled in this study. Features including volumes for cortical structures and subcortical regions, locations and volumes of infarctions, and white matter hyperintensity (WMH) volumes were recorded from all individuals. The impact features were identified using ANCOVA and logistic analysis. Another cohort (n = 21) was further recruited to verify the prognostic roles of screened prognostic structures. Results: For the primary clinical outcome, decreased brainstem volume and total infarction volumes from mesencephalon and midbrain were significantly related to reduced 90-day modified Rankin score (mRS) after MT treatment. WMH volume, WMH grade, average cortex thickness, white matter volume, and gray matter volume did not exhibit a remarkable relationship with the prognosis of BAO. The increased left caudate volume was obviously associated with early symptomatic recovery after MT. The prognostic role of the ratio of pons and midbrain infarct volume in brainstem was further confirmed in another cohort with area under the curve (AUC) = 0.77. Conclusions: This study was the first to provide comprehensive structural markers for the prognostic evaluation of BAO. The fully automatic and semiautomatic segmentation approaches in our study supported that the proportion of mesencephalon and midbrain infarct volume in brainstem was a crucial prognostic structural neural marker for BAO.

10.
Front Neurol ; 12: 527541, 2021.
Article in English | MEDLINE | ID: mdl-34093379

ABSTRACT

Background: Percutaneous transluminal angioplasty and stenting with the Wingspan stent has proven safe and effective in patients with middle cerebral artery stenosis (MCAS), but the off-label use of the Neuroform stent might be an alternative treatment. This study aimed to compare the safety and effectiveness of the above two intracranial stents in patients with MCAS. Methods: We retrospectively analyzed consecutive patients with symptomatic MCAS who had been treated with the Neuroform EZ or the Wingspan stent. A propensity score was generated to control for differences in baseline characteristics. The endpoints were the rate of peri-procedural complications within 30 days after stenting, the in-stent restenosis rate, and any target-vessel-related stroke or deaths during follow-up. Results: After matching for propensity score, the peri-procedural complication rate in the Wingspan group was 7.4% compared with 5.6% in the Neuroform group (p = 1.00), while the follow-up in-stent restenosis rates were 23.3 vs. 14.3%, respectively (p = 0.41). In the restenosis group, the patients tended to be younger (p < 0.01) and the degree of artery stenosis before stenting was higher (p < 0.01). Conclusion: This study indicated that in patients with symptomatic MCAS, Neuroform EZ stents are an alternative to Wingspan. Moreover, younger age and higher degree of artery stenosis before stenting might be a risk factor of in-stent restenosis.

11.
Childs Nerv Syst ; 37(1): 253-257, 2021 01.
Article in English | MEDLINE | ID: mdl-32533299

ABSTRACT

PURPOSE: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems. The TSC1 and TSC2 genes have been identified as the genetic basis of TSC. Two gene tests were used for definitive genetic diagnosis. METHODS: In our study, the case of a Chinese pediatric patient with seizures, hypomelanotic macules, hyperpigmented patches, multiple parenchymal lesions in the ventricle, and developmental retardation is detailed. Whole-genome sequencing (WGS) and multiplex ligation-dependent probe amplification (MLPA) were employed to detect genetic variations and copy number variations of TSC1 and TSC2. RESULTS: A novel heterozygous nonsense mutation in the TSC2 gene (c.3751A>T, p.Lys1251Ter) was identified in a Chinese pediatric patient suffering from TSC, whose unaffected parents did not carry this mutation. The mutation was classified as "pathogenic" according to the American College of Medical Genetics (ACMG) guidelines. CONCLUSION: WGS was carried out to definitively diagnose and detect variations in the exon and noncoding region of the gene and copy number variations in the whole genome simultaneously. For diseases with complex genetic mechanisms, WGS as the first-line test can be efficient and cost-effective for clinical diagnosis.


Subject(s)
Codon, Nonsense , Tuberous Sclerosis , Child , DNA Copy Number Variations , Humans , Mutation , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 1 Protein/genetics , Tuberous Sclerosis Complex 2 Protein/genetics
12.
Front Neurosci ; 14: 777, 2020.
Article in English | MEDLINE | ID: mdl-33071720

ABSTRACT

Oxylipins are a series of bioactive lipid metabolites derived from polyunsaturated fatty acids that are involved in cerebral homeostasis and the development of intracerebral hemorrhage (ICH). However, comprehensive quantification of the oxylipin profile in ICH remains unknown. Therefore, an ICH mouse model was constructed and liquid chromatography tandem mass spectrometry was then performed to quantify the change in oxylipins in ICH. The expression of the oxylipin relative enzymes was also reanalyzed based on RNA-seq data from our constructed ICH dataset. A total of 58 oxylipins were quantifiable and the levels of 17 oxylipins increased while none decreased significantly in the first 3 days following ICH. The most commonly increased oxylipins in ICH were derived from AA (10/17) and EPA (4/17) followed by LA (2/17) and DHA (1/17). 18-HEPE from EPA was the only oxylipin that remained significantly increased from 0.5 to 3 days following ICH. Furthermore, 14 of the increased oxylipins reached a peak level on the first day of ICH, and soon decreased while five oxylipins (PGJ2, 15-oxo-ETE, 12-HEPE, 18-HEPE, and 5-oxo-ETE) had increased 3 days after ICH suggesting that the profile shifted with the progression of ICH. In our constructed RNA-seq dataset based on ICH rats, 90 oxylipin relative molecules were detected except for COX. Among these, Cyp4f18, Cyp1b1, Cyp2d3, Cyp2e1, Cyp1a1, ALOX5AP, and PLA2g4a were found up-regulated and Cyp26b1 was found to decrease in ICH. In addition, there was no significant change in sEH in ICH. This study provides fundamental data on the profile of oxylipins and their enzymes in ICH. We found that the profile shifted as the progression of ICH and the metabolism of arachidonic acid and eicosapentaenoic acid was highly affected in ICH, which will help further studies explore the functions of oxylipins in ICH.

13.
Front Neurosci ; 14: 181, 2020.
Article in English | MEDLINE | ID: mdl-32210752

ABSTRACT

RNA-binding proteins (RBPs) have been shown to be involved in posttranscriptional regulation, which plays an important role in the pathophysiology of intracerebral hemorrhage (ICH). Peroxiredoxin 1 (Prdx1), an RBP, plays an important role in regulating inflammation and apoptosis. On the basis that inflammation and apoptosis may contribute to ICH-induced brain injury, in this study, we used ICH models coupled with in vitro experiments, to investigate the role and mechanism of Prdx1 in regulating inflammation and apoptosis by acting as an RBP after ICH. We first found that Prdx1 was significantly up-regulated in response to ICH-induced brain injury and was mainly expressed in astrocytes and microglia in ICH rat brains. After overexpressing Prdx1 by injecting adeno-associated virus (AAV) into the striatum of rats at 3 weeks, we constructed ICH models and found that Prdx1 overexpression markedly reduced inflammation and apoptosis after ICH. Furthermore, RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq) in vitro revealed that Prdx1 affects the stability of inflammation- and apoptosis-related mRNA, resulting in the inhibition of inflammation and apoptosis. Finally, overexpression of Prdx1 significantly alleviated the symptoms and mortality of rats subjected to ICH. Our results show that Prdx1 reduces ICH-induced brain injury by targeting inflammation- and apoptosis-related mRNA stability. Prdx1 may be an improved therapeutic target for alleviating the brain injury caused by ICH.

15.
Pediatr Neurosurg ; 55(1): 26-35, 2020.
Article in English | MEDLINE | ID: mdl-31851997

ABSTRACT

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe subtype of childhood-onset epileptic encephalopathy with drug-resistant and poor surgical prognosis. However, electroencephalogram (EEG) patterns of symptomatic LGS or LG phenotypes with structural brain lesions including focal abnormalities or asymmetric slow-spike-wave (SSW) patterns remain largely unknown. Due to the contradictory lateralization difference between MRI lesions and EEG pattern in symptomatic LGS or LG phenotypes, it is difficult to determine the precise lateralization of epileptic lesions, which is crucial to better surgical prognosis. This study is aim to ascertain the clinical characteristics of the EEG patterns, and its relationship with MRI lesions and to evaluate its prognostic value of surgical treatment in symptomatic LGS or LG phenotypes. METHODS: Twenty-four symptomatic LGS cases with asymmetric EEG SSW patterns and contralaterally independent or contralaterally dominant MRI lesions were collected, and their clinical features were analyzed retrospectively. RESULTS: In this cohort, most of lesions were perinatal or acquired during the first 6 months of life. The most common etiology was intracerebral hemorrhage. The LGS patients with both asymmetric SSW and focal sporadic epileptic waves (SEW) patterns showed the best surgical outcome with Engel class I level. Asymmetric SSW patterns with maximal discharges contralateral to MRI lesions were frequently observed in most of symptomatic LGS or LG phenotypes. Predominantly diffuse destructive lesions led to an attenuated voltage of ipsilateral scalp EEG producing an asymmetric SSW pattern in those patients with symptomatic LGS or LG phenotypes. CONCLUSIONS: Our study reveals a special SEW EEG pattern in symptomatic LG patients with asymmetric SSW and MRI lesions contralateral to the dominant EEG patterns. Contradictory lateralization difference between MRI and EEG probably arises from the relative voltage attenuation presenting in EEG ipsilateral to huge destructive lesions from early life. Our study suggests that the independent focal SEW activity remaining ipsilateral to the MRI lesion can potentially predict better surgical prognosis in symptomatic LGS or LG phenotypes.


Subject(s)
Electroencephalography , Lennox Gastaut Syndrome/diagnosis , Magnetic Resonance Imaging , Adolescent , Child , Child, Preschool , Female , Humans , Intellectual Disability , Male , Phenotype , Prognosis , Retrospective Studies , Young Adult
16.
Medicine (Baltimore) ; 98(46): e17860, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31725627

ABSTRACT

BACKGROUND: Liraglutide is a novel, long-acting glucagon-like peptide-1 (GLP-1) analogue used to treat type 2 diabetes mellitus. However, the cardiovascular safety and benefits of liraglutide treatment on type 2 diabetes patients remain in debate. In this study, we aimed to examine the overall cardiovascular outcomes of liraglutide in patients with type 2 diabetes. METHODS: In this systematic review and meta-analysis, we searched the PubMed, Embase, and Web of Knowledge databases up to September 1st, 2017 for randomized trials in which type 2 diabetes patients were assigned to liraglutide and placebo or other comparators groups. RESULTS: Eight studies fulfilled the eligibility criteria for inclusion and 14,608 patients were analyzed in this systematic review and meta-analysis. We found patients in the liraglutide group had a lower risk of major cardiovascular events (MACE) (RR = 0.89, 95% CI: 0.82-0.96, P = .002), acute myocardial infarction (AMI) (RR = 0.85, 95% CI: 0.74-0.99, P = .036), all-cause death (RR = 0.84, 95% CI: 0.74-0.96, P = .009), and cardiovascular death (RR = 0.77, 95% CI: 0.65-0.91, P = .002) than all comparator groups. However, liraglutide treatment did not decrease incidence of stroke (RR = 0.86, 95% CI: 0.70-1.04, P = .124). But among the MACE subgroups analysis, a significant reduction of MACE with liraglutide was only observed in placebo-controlled trials (RR = 0.89, 95% CI: 0.83-0.96, P = .004) but not in studies concerning other comparators (RR = 0.58, 95% CI: 0.29-1.16, P = .122). CONCLUSIONS: In conclusion, our results suggest that liraglutide treatment decreases the risk of MACE, AMI, all-cause death and cardiovascular death among patients with type 2 diabetes.


Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Liraglutide/therapeutic use , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/mortality , Humans , Hypoglycemic Agents/therapeutic use , Myocardial Infarction/epidemiology , Randomized Controlled Trials as Topic , Stroke/epidemiology
17.
Biosci Rep ; 39(5)2019 05 31.
Article in English | MEDLINE | ID: mdl-31040201

ABSTRACT

Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.


Subject(s)
Aging/metabolism , Brain Injuries/metabolism , Brain/metabolism , Cerebral Hemorrhage/metabolism , Plasma/metabolism , Adult , Aged , Aging/drug effects , Animals , Brain/drug effects , Brain Injuries/drug therapy , Cerebral Hemorrhage/drug therapy , Disease Models, Animal , Female , Humans , Insulin-Like Growth Factor I/metabolism , Male , Mice , Mice, Inbred C57BL , Middle Aged , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
18.
J Clin Neurosci ; 63: 17-21, 2019 May.
Article in English | MEDLINE | ID: mdl-30850180

ABSTRACT

This retrospective study is to investigate the safety and efficacy of the stent implanting for treating severe symptomatic atherosclerotic stenosis of the intracranial vertebrobasilar artery (ICVBA). 213 patients who had undergone intervention for severe symptomatic ICVBA stenosis between September 2012 to May 2018 were enrolled into this study. Among the 213 enrolled patients, 210 patients (98.6%) obtained successfully revascularization and 206 patients (96.7%) had good revascularization after stenting. The extent of stenosis before and after intervention was 86.3 ±â€¯6.8% and 9.1 ±â€¯3.7%, respectively. Within 90 days after stenting, 10 patients (4.7%) experienced primary endpoint events, including 4 cases (4.2%) in the intracranial vertebral artery (V4) group and 6 (5.1%) in basilar artery (BA) group. Among them, 2 (2.1%) and 3 cases (2.5%) of ischemic stroke in V4 and BA group, respectively; and 2 (2.1%) and 2 (1.7%) cases of TIA in V4 and BA group, respectively. One (0.8%) case in the BA group dead because of the acute stent occlusion resulted in the top of the basilar syndrome. Six patients (2.8%) experienced adverse events, including 2 (2.1%) and 4 (3.4%) cases of groin hematoma in the V4 and BA group, respectively. No cases of hemorrhagic stroke, stent dislocation and vessel dissection in both groups. Our study showed that a low complication rate and a high and good revascularization rate would be achieved by the treatment of severe symptomatic atherosclerotic stenosis of the ICVBA using the stents.


Subject(s)
Angioplasty/adverse effects , Intracranial Hemorrhages/epidemiology , Postoperative Complications/epidemiology , Stents/adverse effects , Stroke/epidemiology , Vertebrobasilar Insufficiency/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Atherosclerosis/complications , Atherosclerosis/surgery , Female , Humans , Intracranial Hemorrhages/etiology , Male , Middle Aged , Stroke/etiology , Vertebrobasilar Insufficiency/etiology
19.
Front Neurol ; 9: 249, 2018.
Article in English | MEDLINE | ID: mdl-29740385

ABSTRACT

Pathophysiological processes of stroke have revealed that the damaged brain should be considered as an integral structure to be protected. However, promising neuroprotective drugs have failed when translated to clinical trials. In this review, we evaluated previous studies of neuroprotection and found that unsound patient selection and evaluation methods, single-target treatments, etc., without cerebral revascularization may be major reasons of failed neuroprotective strategies. Fortunately, this may be reversed by recent advances that provide increased revascularization with increased availability of endovascular procedures. However, the current improved effects of endovascular therapy are not able to match to the higher rate of revascularization, which may be ascribed to cerebral ischemia/reperfusion injury and lacking of neuroprotection. Accordingly, we suggest various research strategies to improve the lower therapeutic efficacy for ischemic stroke treatment: (1) multitarget neuroprotectant combinative therapy (cocktail therapy) should be investigated and performed based on revascularization; (2) and more efforts should be dedicated to shifting research emphasis to establish recirculation, increasing functional collateral circulation and elucidating brain-blood barrier damage mechanisms to reduce hemorrhagic transformation. Therefore, we propose that a comprehensive neuroprotective strategy before and after the endovascular treatment may speed progress toward improving neuroprotection after stroke to protect against brain injury.

20.
J Clin Neurosci ; 53: 165-170, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29754966

ABSTRACT

Intracranial aneurysm (IA) is a common lesion which often present asymptomatic until the time of rupture and result in subarachnoid hemorrhage (SAH). The pathogenesis of IA formation is complex and is influenced by both genetic and environmental risk factors. For exploring the detailed molecular and cellular mechanisms involved in the pathogenesis of IA, recent studies indicated inflammatory pathways and their genetic variants may as potential biomarkers. In this study, functionally relevant polymorphisms in the toll-like receptor 4 (TLR4) were screened in 330 IA patients and 313 controls from a Han Chinese population. Eight single nucleotide gene polymorphisms (SNPs) genotyped by the Improved Multiple Ligase Detection Reaction (iMLDR) method. Our results indicated that the presence of the minor allele (C) of the TLR4 SNP rs11536889 was associated with a decreased risk of IA (C vs. G, OR = 0.731; 95% CI 0.567-0.943; P = 0.017). This association was also present at the genotype level in a codominant model (GC vs. GG, OR = 0.447; 95% CI 0.226-0.884; P = 0.020) and a recessive model (CC vs. GG + GC, OR = 0.489; 95% CI 0.250-0.955; P = 0.035). In summary, we firstly found that the TLR4 SNP rs11536889 was significantly associated with the susceptibility of IA. Our results indicated TLR4 SNP rs11536889 may be a marker for IA risk, though the exact functional roles of TLR4 SNP rs11536889 in IA formation are still not very clear.


Subject(s)
Genetic Predisposition to Disease/genetics , Intracranial Aneurysm/genetics , Toll-Like Receptor 4/genetics , Adult , Asian People/genetics , Biomarkers/analysis , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Young Adult
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