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Neuroscience. Stem cells hear call of injured tissue.

In animal models, injected stem cells travel to tissue injured by stroke, Alzheimer's-like plaques, contusions, or spinal cord bruises, sometimes traversing long distances. Several teams reported these surprising results this month at the Society for Neuroscience annual meeting. No one knows exactly how stem cells detect these different kinds of damage, but researchers hope that the cells' migratory powers can be harnessed to either replace dead tissue or deliver therapeutics right where they're needed.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in … different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was appro …

TOMM40 suppression promotes neuronal cholesterol imbalance and molecular and behavioral phenotypes of Alzheimer's disease.

INTRODUCTION: While the apolipoprotein E (APOE) ε4 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (TOMM40)-an adjacent gene involved in mitochondrial protein import-is not known. METHODS: Human brain tissue, human induced pluripotent stem cell-derived neurons (iNeurons), and mice were used for study of gene expression, cholesterol metabolism, mitochondrial function, and animal cognition. RESULTS: Human brain transcriptomics showed reduced TOMM40 expression that correlated with cholesterol regulatory gene expression, amyl

Loss of EB2 delays mitotic progression in murine and human neural progenitors.

The construction of the human brain is dependent on neuronal progenitors that divide accurately generating billions of neurons. This neurogenic potential requires the efficient assembly of the mitotic spindle, which mediates the alignment of sister chromatids and their subsequent separation. The mitotic spindle is formed from microtubules, which are decorated with proteins that alter the functional repertoire of the cytoskeleton. Mutations in EB2, a member of the end binding protein family, have been identified in individuals with multiple congenital defects including microcephaly. Here, we co

Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of rare genetic neurodegenerative disorders characterized by corticospinal tract abnormalities. But frequently, abnormalities of proteins implicated in HSP have been identified in brain disorders of childhood, raising the possibility that early brain developmental mechanism underlying HSP. RESULTS AND CONCLUSIONS: Here we summarized the clinical features of 89 HSP subtypes and found most have onset of symptoms earliest reported in infancy or early childhood. Importantly, HSP patients showed early brain developmental related phenotypes

Применение глубокой стимуляции мозга в случае множественных склерозовых треморов и новых целевых показателей: мини-обзор.

Множественные склерозы (MS), которые являются общей причиной инвалидности, не всегда реагируют на фармакологическое лечение. В противоположность этому, глубокая стимуляция головного мозга (БРС) в таламических или субфаламических районах (особенно в zona incerta, ZI) вызвала реакцию в подавлении дрожжей MS. В этом исследовании мы искали соответствующую литературу для дальнейшего изучения позитивных и негативных последствий использования DBS, посаженных в различных районах мозга, для подавления дрожжей MS. Уникальные эффекты GABAergic агентов из ZI связаны как с базальными ганглией таламокортным

Совпадение в аннотации оригинала
Multiple sclerosis (MS) tremors, which are a common cause of disability, do not always respond to pharmacological treatment. Contrastingly, … to both the basal ganglia thalamocortical and cerebellar thalamocortical loops, in addition to the brain stem motor effector, where tremor oscillation may be transmitted. From this, the ZI is an effective target for ameliorating MS tremors through surgical treatment. Stimulation of the ZI, even bilaterally, could better control MS tremors, and with fewer si …

Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.

The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes an

A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors.

The natural compound Artemisinin is the most widely used antimalarial drug worldwide. Based on its cytotoxicity, it is also used for anticancer therapy. Artemisinin and its derivates are endoperoxides that damage proteins in eukaryotic cells; their definite mechanism of action and host cell targets, however, have remained largely elusive. Using yeast and haploid stem cell screening, we demonstrate that a single cellular pathway, namely porphyrin (heme) biosynthesis, is required for the cytotoxicity of Artemisinins. Genetic or pharmacological modulation of porphyrin production is sufficient to

Acute albumin administration as therapy for intracerebral hemorrhage: A literature review.

Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality. Secondary brain injury after surviving the initial ictus leads to severe neurological deficits, and has emerged as an attractive therapeutic target. Human serum albumin (HSA), a pluripotent protein synthesized mainly in the liver, has shown remarkable efficacy by targeting secondary brain injury pathways in rodent models of ICH, while results from relevant clinical research on albumin therapy remain unclear. Preclinical studies have shown albumin-mediated neuroprotection may stem from its biological functions, including

Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2 Variant.

Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent. However, a missense variant in RANBP2 has been identified in some families with recurrent AN…

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury.

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need ther

[Dural Arteriovenous Fistula].

Dural arteriovenous fistulas(dAVFs), which are arteriovenous shunts between the dural/epidural artery and dural vein and/or dural venous sin … sment using CT/MRI to prevent further worsening of symptoms, particularly for lesions involving the brain stem and cerebellum.

Report: Cytotoxic activity of phytochemicals from the stem bark of Calophyllum castaneum.

Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain

White Matter Repair After Extracellular Vesicles Administration in an Experimental Animal Model of Subcortical Stroke.

Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics.

Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 i

Reward deficiency and anti-reward in pain chronification.

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in … nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as an …

A Novel CXCR4 Antagonist CX549 Induces Neuroprotection in Stroke Brain.

C-X-C chemokine receptor type 4 (CXCR4) is a receptor for a pleiotropic chemokine CXCL12. Previous studies have shown that the acute administration of the CXCR4 antagonist AMD3100 reduced neuroinflammation in stroke brain and mobilized bone marrow hematopoietic stem cells (HSCs). The purpose of this study was to characterize the neuroprotective and neurotrophic effect of a novel CXCR4 antagonist CX549. We demonstrated that CX549 had a higher affinity for CXCR4 and was more potent than AMD3100 to inhibit CXCL12-mediated chemotaxis in culture. CX549 effectively reduced the activation of microgli

Development of primary central nervous system lymphoma associated with human immunodeficiency virus and JC virus infection.

We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primar … he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.

Platelet lysates stimulate angiogenesis, neurogenesis and neuroprotection after stroke.

Platelets contain chemo-attractants and mitogens that have a major role in tissue repair. Therefore we hypothesised that tissue regeneration secondary to activation of endogenous neural stem cells (eNSC) can be enhanced by delivering platelets to the ischaemic brain. To examine these potential therapeutic effects we injected platelet-poor plasma (PPP), fibroblast growth factor (FGF2) and platelet lysate (PLT) to the lateral ventricles after permanent middle cerebral artery occlusion (PMCAO) in rats. The animals were tested with the neurological severity score, and infarct volumes were measured

Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke.

Stroke is a leading cause of disability with no effective regenerative treatment. One promising strategy for achieving tissue repair involves the stimulation of endogenous neural stem/progenitor cells through sequential delivery of epidermal growth factor (EGF) followed by erythropoietin (EPO). Yet currently available delivery strategies such as intracerebroventricular (ICV) infusion cause significant tissue damage. We designed a novel delivery system that circumvents the blood brain barrier and directly releases growth factors to the brain. Sequential release of the two growth factors is a ke