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Ferroptosis, a Recent Defined Form of Critical Cell Death in Neurological Disorders
AbstractFerroptosis is a recently defined form of cell death with the involvement of iron and reactive oxygen species (ROS), which is distinct from apoptosis, autophagy and other forms of cell death. Emerging evidence suggested that iron accumulation and lipid peroxidation can be discovered in various neurological diseases, accompanied with reduction of glutathione (GSH) and glutathione peroxidase 4 (GPX4). In addition, ferroptotic inhibitors have been shown to protect neurons, and recover the cognitive function in disease animal models. This review summarizes the mechanisms underlying ferroptosis and reviews the contribut...
Source: Journal of Molecular Neuroscience - August 25, 2018 Category: Neuroscience Source Type: research

Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury
AbstractResearch into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatu...
Source: Journal of Molecular Neuroscience - September 3, 2018 Category: Neuroscience Source Type: research

Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced Hippocampal Damage in Rats
AbstractStroke is the second leading reason for death worldwide and is one of the fundamental causes of long-term disabilities. The aim of this investigation was to assess the impact of combined administration progesterone (PROG) and melatonin (MEL) on stroke complications. Male Wistar rats (9 –10 weeks) weighing 250–300 g were used as a part of this examination. They were randomly separated into eight groups (nine rats for every group). Common carotid arteries on the two sides clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the rats were treated with 8 m g/kg PROG, 10 mg/kg MEL, and vehi...
Source: Journal of Molecular Neuroscience - September 4, 2018 Category: Neuroscience Source Type: research

Genetic Variation of the Kalirin Gene is Associated with ICAS in the Chinese Population
AbstractIntracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke (IS), especially in recurrent patients. Several studies have demonstrated an intimate association between the genetic mutation of theKALRN gene and IS. The main aim of this study was to clarify the relationship between three single nucleotide polymorphisms (SNPs) ofKALRN and ICAS in a northern Chinese population and further explore the underlining mechanism. The relationship between each SNP and ICAS and the related components were examined in five models (co-dominant, dominant, recessive, heterozygous, and additive). M...
Source: Journal of Molecular Neuroscience - September 19, 2018 Category: Neuroscience Source Type: research

Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury
AbstractResearch into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatu...
Source: Journal of Molecular Neuroscience - October 1, 2018 Category: Neuroscience Source Type: research

Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced Hippocampal Damage in Rats
AbstractStroke is the second leading reason for death worldwide and is one of the fundamental causes of long-term disabilities. The aim of this investigation was to assess the impact of combined administration progesterone (PROG) and melatonin (MEL) on stroke complications. Male Wistar rats (9 –10 weeks) weighing 250–300 g were used as a part of this examination. They were randomly separated into eight groups (nine rats for every group). Common carotid arteries on the two sides clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the rats were treated with 8 m g/kg PROG, 10 mg/kg MEL, and vehi...
Source: Journal of Molecular Neuroscience - October 1, 2018 Category: Neuroscience Source Type: research

Ferroptosis, a Recent Defined Form of Critical Cell Death in Neurological Disorders
AbstractFerroptosis is a recently defined form of cell death with the involvement of iron and reactive oxygen species (ROS), which is distinct from apoptosis, autophagy and other forms of cell death. Emerging evidence suggested that iron accumulation and lipid peroxidation can be discovered in various neurological diseases, accompanied with reduction of glutathione (GSH) and glutathione peroxidase 4 (GPX4). In addition, ferroptotic inhibitors have been shown to protect neurons, and recover the cognitive function in disease animal models. This review summarizes the mechanisms underlying ferroptosis and reviews the contribut...
Source: Journal of Molecular Neuroscience - October 1, 2018 Category: Neuroscience Source Type: research

Biomarker and Drug Target Discovery Using Quantitative Proteomics Post-Intracerebral Hemorrhage Stroke in the Rat Brain
AbstractThe pathological mechanisms of acute intracerebral hemorrhage (ICH) remain unknown and unverified. In the present study, we used quantitative proteomics to elucidate the pathological mechanisms and to identify novel biomarker and therapeutic target candidates via tissue proteome in a rat model of acute ICH. Rats were experimentally induced with ICH (n = 6) or Sham (n = 6), and their brain tissue was obtained by 24 h. The TMT-LC–MS/MS-based proteomics approach was used to quantify the differential proteomes across brain tissue, and the results were further analyzed by ingenuity pathway analysis to explore...
Source: Journal of Molecular Neuroscience - November 14, 2018 Category: Neuroscience Source Type: research

Non-invasive Vagus Nerve Stimulation Protects Against Cerebral Ischemia/Reperfusion Injury and Promotes Microglial M2 Polarization Via Interleukin-17A Inhibition
In conclusion, our study identifies microglial M2 polarization as an important mechanism underlying the nVNS-mediated neuroprotection against cerebral I/R. This effect of nVNS could be attributed to the inhibition of IL-17A expression.
Source: Journal of Molecular Neuroscience - November 27, 2018 Category: Neuroscience Source Type: research

miR-34a in Neurophysiology and Neuropathology
AbstractEpigenetic influence of brain and neuronal function plays key regulatory roles in health and diseases. The microRNA miR-34a is a tumor suppressor transcript, and its loss has been prominently linked to various human cancers, including malignancies of the brain. Interestingly, miR-34a is abundantly expressed in the adult mammalian brain, and emerging evidence has implicated its involvement in a range of neurodevelopmental and neuropathological processes. Developmentally, miR-34a regulates neural stem/progenitor cell differentiation and aspects of neurogenesis. During aging, its elevation is connected to hearing loss...
Source: Journal of Molecular Neuroscience - November 28, 2018 Category: Neuroscience Source Type: research

Dietary Energy Restriction Ameliorates Cognitive Impairment in a Mouse Model of Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is one of the most common causes of neurological damage in young people. It was previously reported that dietary restriction, by either intermittent fasting (IF) or daily caloric restriction (CR), could protect neurons against dysfunction and degeneration in animal models of stroke and Parkinson ’s disease. Recently, several studies have shown that the protein Sirtuin 1 (SIRT1) plays a significant role in the induced neuroprotection following dietary restriction. In the present study, we found a significant reduction of SIRT1 levels in the cortex and hippocampus in a mouse model of mi...
Source: Journal of Molecular Neuroscience - February 8, 2019 Category: Neuroscience Source Type: research

Ghrelin Promotes Cortical Neurites Growth in Late Stage After Oxygen-Glucose Deprivation/Reperfusion Injury
In this study, we explored the effects of acyl ghrelin on cultured organotypic brain slices and cortical neurons which were injured by oxygen–glucose deprivation/reperfusion(OGD/ R) for 7 days. The underlying molecular mechanisms were deciphered based on label-free proteomic analysis. Acyl ghrelin treatment promoted neurite (axons and dendrites) growth and alleviated the neuronal damage in both cultured brain slices and neurons. Proteomic analysis showed that cell division control protein 42 (Cdc42) mediates the effects of acyl ghrelin on neurite growth. Acyl ghrelin stimulated the expression of Cdc42 and neurite growth...
Source: Journal of Molecular Neuroscience - February 26, 2019 Category: Neuroscience Source Type: research

Angiogenic Gene Profiles in Laser-Microdissected Microvessels and Neurons from Ischemic Penumbra of Rat Brain
AbstractAngiogenesis is induced immediately after cerebral ischemia and plays a pivotal role in the strategy against ischemic injury. We hypothesized that the coordinated interaction between microvessels and neurons was altered immediately after stroke, and microvessels and neurons would show the temporal specificity of angiogenic gene profiles after cerebral ischemia. Microvessels and neurons were harvested in the ischemic penumbra of rat brain using the PixCell II laser capture microdissection (LCM) instrument. After RNA isolation, T7 and gene-specific primer RNA linear amplification were performed, and angiogenic functi...
Source: Journal of Molecular Neuroscience - March 5, 2019 Category: Neuroscience Source Type: research

Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats
AbstractLong-term memory impairment is reported in more than 50% of cardiac arrest survivors. Monosialoganglioside (GM1) provided neuroprotection in experimental models of stroke but failed to replicate its promise clinically for unknown reasons. GM1 stimulates the release of nerve growth factor (NGF), which is synthesized as a precursor protein (pro-NGF) that either mediates apoptosis through the p75 neurotrophin receptor (p75NTR) or is cleaved by the protease furin (FUR) to yield mature NGF, the latter supporting survival through tropomyosin kinase receptor (Trk). The flavanol epicatechin (EPI) inhibits p75NTR-mediated s...
Source: Journal of Molecular Neuroscience - March 11, 2019 Category: Neuroscience Source Type: research

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