Increased Cell Fusion in Cerebral Cortex May Contribute to Poststroke Regeneration

In this study, we used a model of a hemorrhagic stroke in a motor zone of the cortex in rats at the age of 3 months The report shows that cortical neurons can fuse with oligodendrocytes. In formed binuclear cells, the nucleus of an oligodendrocyte undergoes neuron specific reprogramming. It can be confirmed by changes in chromatin structure and in size of the second nucleus, by expression of specific neuronal markers and increasing total transcription rate. The nucleus of an oligodendrocyte likely transforms into a second neuronal nucleus. The number of binuclear neurons was validated with quantitative analysis. Fusion of neurons with oligodendrocytes might be a regenerative process in general and specifically following a stroke. The appearance of additional neuronal nuclei increases the functional outcome of the population of neurons. Participation of a certain number of binuclear cells in neuronal function might compensate for a functional deficit that arises from the death of a subset of neurons. After a stroke, the number of binuclear neurons increased in cortex around the lesion zone. In this case, the rate of recovery of stroke-damaged locomotor behavior also increased, which indicates the regenerative role of fusion.

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Application of a free radical scavenger edaravone in patients with hemorrhagic stroke

Infusion & Chemotherapy ◽

10.32902/2663-0338-2021-1-28-36 ◽

2021 ◽

pp. 28-36

Author(s):

O.A. Halushko

Keyword(s):

Free Radical ◽

Intracerebral Hemorrhage ◽

Hemorrhagic Stroke ◽

Hemorrhagic Transformation ◽

Free Radical Scavenger ◽

Neurological Deficits ◽

Radical Scavenger ◽

Rate Of Recovery ◽

Main Effects

BACKGROUND. The free radical scavenger edaravone helps to reduce the area of ischemic injury and improve the longterm effects of stroke, and is therefore widely used in the treatment of ischemic stroke. However, the role of edaravone in the treatment of hemorrhagic stroke patients has not yet been clarified. OBJECTIVE. To investigate the feasibility and effectiveness of the use of the free radical scavenger edaravone in the treatment of patients with acute hemorrhagic stroke. MATERIALS AND METHODS. A search was conducted for studies and systematic reviews for the keywords “acute stroke”, “intracerebral hemorrhage”, “subarachnoid hemorrhage”, “hemorrhagic transformation”, “edaravone” in the Google Scholar database published between 2003 and 2020. RESULTS. The use of edaravone in patients with intracerebral hemorrhage was accompanied by activation of anti-inflammatory and reduction of pro-inflammatory peptides, activation of anti-apoptotic mechanisms, reduction of lipid peroxidation and oxidative trauma, reduction of permeability of the hematocenosis. CONCLUSIONS. The main effects of edaravone have been to reduce neurological deficits, accelerate the rate of recovery of neurological disorders, and improve functional outcomes. Thus, the introduction of edaravone in patients with hemorrhagic stroke has proven to be reliably effective and safe.

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Faculty Opinions recommendation of A dual role of EphB1/ephrin-B3 reverse signaling on migrating striatal and cortical neurons originating in the preoptic area: should I stay or go away?

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726218366.793515751 ◽

2016 ◽

Author(s):

Karina Cramer

Keyword(s):

Cortical Neurons ◽

Preoptic Area ◽

Dual Role ◽

Reverse Signaling

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Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

Journal of Alzheimer s Disease ◽

10.3233/jad-201472 ◽

2021 ◽

pp. 1-15

Author(s):

Vasily Vorobyov ◽

Alexander Deev ◽

Frank Sengpiel ◽

Vladimir Nebogatikov ◽

Aleksey A. Ustyugov

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Cortical Neurons ◽

Primary Motor Cortex ◽

Beta Activity ◽

Systemic Injection ◽

Eeg Spectra ◽

Electroencephalogram Eeg ◽

Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

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Subcortical circuits mediate communication between primary sensory cortical areas in mice

Nature Communications ◽

10.1038/s41467-021-24200-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Michael Lohse ◽

Johannes C. Dahmen ◽

Victoria M. Bajo ◽

Andrew J. King

Keyword(s):

Cortical Neurons ◽

Common Property ◽

Primary Auditory Cortex ◽

Facilitatory Effect ◽

Thalamic Nuclei ◽

Auditory Midbrain ◽

Cortical Areas ◽

Auditory Responses ◽

Evoked Activity

AbstractIntegration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.

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F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽

10.3390/molecules26082231 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2231

Author(s):

Qingjun Lu ◽

Hao Shen ◽

Han Yu ◽

Jing Fu ◽

Hui Dong ◽

...

Keyword(s):

Liver Regeneration ◽

Serum Levels ◽

Inhibitory Effect ◽

Regenerative Process ◽

Oncostatin M ◽

Hepatocyte Proliferation ◽

Initiation Phase ◽

Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

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Ndufs4 ablation decreases synaptophysin expression in hippocampus

Scientific Reports ◽

10.1038/s41598-021-90127-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Subrata Kumar Shil ◽

Yoshiteru Kagawa ◽

Banlanjo Abdulaziz Umaru ◽

Fumika Nanto-Hara ◽

Hirofumi Miyazaki ◽

...

Keyword(s):

Nadh Dehydrogenase ◽

Leigh Syndrome ◽

Mitochondrial Respiratory Chain ◽

Mitochondrial Activity ◽

Mitochondrial Complex ◽

Neuronal Function ◽

Mouse Hippocampus ◽

Extracellular Regulated Kinase ◽

Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

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Cardiac regeneration: epicardial mediated repair

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2147 ◽

2015 ◽

Vol 282 (1821) ◽

pp. 20152147 ◽

Cited By ~ 17

Author(s):

Teresa Kennedy-Lydon ◽

Nadia Rosenthal

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Cardiac Fibroblasts ◽

Cardiac Regeneration ◽

Repair Process ◽

Regenerative Process ◽

Cardiac Stem Cell ◽

Cardiomyocyte Proliferation ◽

Lower Vertebrates

The hearts of lower vertebrates such as fish and salamanders display scarless regeneration following injury, although this feature is lost in adult mammals. The remarkable capacity of the neonatal mammalian heart to regenerate suggests that the underlying machinery required for the regenerative process is evolutionarily retained. Recent studies highlight the epicardial covering of the heart as an important source of the signalling factors required for the repair process. The developing epicardium is also a major source of cardiac fibroblasts, smooth muscle, endothelial cells and stem cells. Here, we examine animal models that are capable of scarless regeneration, the role of the epicardium as a source of cells, signalling mechanisms implicated in the regenerative process and how these mechanisms influence cardiomyocyte proliferation. We also discuss recent advances in cardiac stem cell research and potential therapeutic targets arising from these studies.

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The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

Clinical and Developmental Immunology ◽

10.1155/2013/939786 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

Elisa Ridolfi ◽

Cinzia Barone ◽

Elio Scarpini ◽

Daniela Galimberti

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Lobar Degeneration ◽

Environmental Changes ◽

Current Evidence ◽

Neuronal Function ◽

Immune Effector ◽

Effector Cells ◽

The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

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