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Repurposing Vorinostat for the Treatment of Disorders Affecting Brain
AbstractBased on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer ’s disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X‐linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric dis...
Source: NeuroMolecular Medicine - December 1, 2021 Category: Neurology Source Type: research

Ferrostatin-1 Alleviates White Matter Injury Via Decreasing Ferroptosis Following Spinal Cord Injury
AbstractSpinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role...
Source: Molecular Neurobiology - October 12, 2021 Category: Neurology Source Type: research

Arterial Ischemic Stroke —Peculiarities of Clinical Presentation and Risk Factors in Indian Children
Neuropediatrics DOI: 10.1055/s-0041-1728773There are not enough recent studies on arterial ischemic stroke (AIS) in Indian children. We retrospectively reviewed data on 95 children (69 boys), aged 3 months to 17 years, with AIS. Focal signs were noted in 84 (88%) with hemiparesis in 72 (76%). Diffuse signs were present in 33 (35%) with fever in 22 (23%), altered mental status in 20 (21%), and headache in 12 (13%). Seizures occurred in 29 (31%) children. Arteriopathy was observed in 57 (60%) children with mineralizing lenticulostriate vasculopathy (mLSV) in 22 (23%) being the most common, followed by moyamoya in 14 (15%), a...
Source: Neuropediatrics - June 8, 2021 Category: Neurology Authors: Goraya, Jatinder Singh Berry, Shivankshi Kaur, Amandeep Singh, Gagandeep Tags: Original Article Source Type: research

Repurposing Vorinostat for the Treatment of Disorders Affecting Brain
AbstractBased on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer ’s disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X‐linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric dis...
Source: NeuroMolecular Medicine - May 4, 2021 Category: Neurology Source Type: research

Electroacupuncture Ameliorates Cerebral Ischemic Injury by Inhibiting Ferroptosis
Conclusion: Our results indicate that EA can inhibit ferroptosis by regulating oxidative stress and iron-related proteins, thus conferring protection against MCAO in a rat model.
Source: Frontiers in Neurology - March 8, 2021 Category: Neurology Source Type: research

Iron Measured in Nasal Exudate Samples as a New and Useful Biomarker in the Differential Diagnosis of Patients with Acute Stroke
Conclusions: Our findings suggest that iron levels in nasal exudate may be useful in the acute stage for the differential diagnosis between ischemic and hemorrhagic damage in acute stroke patients. They also open a potential field to study other biomarkers in nasal exudate in several neurological disorders. Clinical studies must be performed to confirm our results.Cerebrovasc Dis
Source: Cerebrovascular Diseases - November 20, 2020 Category: Neurology Source Type: research

Epigenetic regulators of neuronal ferroptosis identify novel therapeutics for neurological diseases: HDACs, transglutaminases, and HIF prolyl hydroxylases.
Abstract A major thrust of our laboratory has been to identify how physiological stress is transduced into transcriptional responses that feed back to overcome the inciting stress or its consequences, thereby fostering survival and repair. To this end, we have adopted the use of an in vitro model of ferroptosis, a caspase-independent, but iron-dependent form of cell death (Dixon et al., 2012; Ratan, 2020). In this review, we highlight three distinct epigenetic targets that have evolved from our studies and which have been validated in vivo studies. In the first section, we discuss our studies of broad, pan-selecti...
Source: Neurobiology of Disease - October 27, 2020 Category: Neurology Authors: Rroji O, Kumar A, Karuppagounder SS, Ratan RR Tags: Neurobiol Dis Source Type: research

Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis
This study aimed to determine the impact of iron chelation with deferoxamine (DFX) on (1) cerebral vascularization patterns and (2) functional outcomes after stroke in control and diabetic rats. After 8  weeks of type 2 diabetes induced by a combination of high-fat diet and low-dose streptozotocin, male control and diabetic animals were subjected to thromboembolic middle cerebral artery occlusion (MCAO) and randomized to vehicle, DFX, or tPA/DFX and followed for 14 days with behavioral tests. Vas cular indices (vascular volume and surface area), neurovascular remodeling (AQP4 polarity), and microglia activation were meas...
Source: Translational Stroke Research - August 31, 2020 Category: Neurology Source Type: research

Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.
Abstract Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to e...
Source: Neurotoxicology - April 28, 2020 Category: Neurology Authors: Van Dyke N, Yenugadhati N, Birkett NJ, Lindsay J, Turner MC, Willhite CC, Krewski D Tags: Neurotoxicology Source Type: research

Association between Anemia and Dementia-A Nationwide, Population-Based Cohort Study in Taiwan.
CONCLUSION: The present population-based cohort study identified that newly diagnosed anemia is a risk factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people with iron deficiency anemia. PMID: 32183675 [PubMed - as supplied by publisher]
Source: Current Alzheimer Research - March 15, 2020 Category: Neurology Authors: Hong CT, Hsieh YC, Liu HY, Chiou HY, Chien LN Tags: Curr Alzheimer Res Source Type: research

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning
AbstractExact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48  h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Decision...
Source: Translational Stroke Research - January 13, 2020 Category: Neurology Source Type: research

Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model
This study was performed to investigate the noninvasive neuroimaging method for quantifying brain iron content using a minipig ICH model and assess the effects of minocycline treatment on ICH-induced iron overload and brain injury. The minipig ICH model was established by injecting 2  ml of autologous blood into the right basal ganglia, which were then subjected to the treatments of minocycline and vehicle. Furthermore, the quantitative susceptibility mapping (QSM) was used to quantify iron content, and diffusion tensor imaging (DTI) was performed to evaluate white matter tract . Additionally, we also performed immunohist...
Source: Translational Stroke Research - November 5, 2019 Category: Neurology Source Type: research

CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats
This study expands those findings by examining the effects on a CD47 blocking antibody in aged rats. First, male Fischer 344 rats (18 months old) received an intracaudate injection of 50 μL auto logous whole blood or saline. Hematoma features of magnetic resonance imaging (MRI) and neurological deficits were evaluated within 3 days. Second, rats had an intracaudate co-injection of 50 μL autologous blood with either CD47 blocking antibody or IgG. MRI was used to quantify hematoma/iron vol ume, hemolysis, brain swelling, and atrophy at different time points, behavioral tests to assess neurological deficits, and immunoh...
Source: Translational Stroke Research - October 29, 2019 Category: Neurology Source Type: research

A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease
AbstractCavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1,CCM2, andCCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to explore the use of a ROCK2-selective kinase inhibitor to reduce growth and hemorrhage of CAs. The role of ROCK2 in CA was investigated by crossingRock1 orRock2 hemizygous mice withCcm1 orCcm3 hemizygous mice, and we found reduced lesions in theRock2 hemizygous mice. A ROCK2-selective inhibitor, BA-1049 wa...
Source: Translational Stroke Research - August 23, 2019 Category: Neurology Source Type: research

Inhibition of neuronal ferroptosis in the acute phase of intracerebral hemorrhage shows long-term cerebroprotective effects.
In this study, we examined whether ICH-induced neuron death is partly ferroptotic in humans and assessed its temporal and spatial characteristics in mice. Furthermore, the ferroptosis inhibitor ferrostatin-1 (Fer-1) was used to examine the role of ferroptosis after ICH. Fold changes in ferroptosis-related gene expression, intracellular iron levels, malondialdehyde (MDA) levels, and both protein levels and cellular localization of cyclooxygenase-2 (COX-2) were measured to monitor ferroptosis. Transmission electron microscopy (TEM) was also performed to examine the ultrastructure of cells after ICH. We found that the express...
Source: Brain Research Bulletin - August 19, 2019 Category: Neurology Authors: Chen B, Chen Z, Liu M, Gao X, Cheng Y, Wei Y, Wu Z, Cui D, Shang H Tags: Brain Res Bull Source Type: research

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