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Immunohistochemical expression of fibroblast growth factor (FGF)-2 in epilepsy-associated malformations of cortical development (MCDs).

To elucidate the biological significance of dysplastic cells in malformations of cortical development, an immunohistochemical study was performed to investigate fibroblast growth factor-2 (FGF-2) expression in corticectomy specimens from epilepsy patients, including focal cortical dysplasia (FCD) with balloon cells (BCs) (n=4; age/sex=2M, 14F, 24M, 45M), tubers of tuberous sclerosis complex (TSC-tubers) (n=2; 1F, 3F), FCD without BCs (n=3; 23F, 23M, 25M), and gliotic lesions (n=3; 12M, 25M, 29M). The nucleus and/or cytoplasm of astrocytes in all cases examined were positive for FGF-2; however,…

Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within … ctory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. …

Differential neuroprotection from human heat shock protein 70 overexpression in in vitro and in vivo models of ischemia and ischemia-like conditions.

We previously showed that overexpressing the 70-kDa inducible heat shock protein in primary astrocyte cultures and in a rodent stroke model … significant difference in glutathione levels between heat shock protein 70 transgenic and wildtype astrocytes. Hippocampal, but not cortical neuron cultures from these same transgenic mice were also protected against oxygen-glucose deprivation and glutamate toxicity. In an in vivo model of permanent focal cerebral ischemia, there was no significant differen …

Dysregulation of signal transduction pathways as a potential mechanism of nervous system alterations in HIV-1 gp120 transgenic mice and humans with HIV-1 encephalitis.

HIV-1 associated central nervous system (CNS) disease involves neuronal damage and prominent reactive astrocytosis, the latter characterized by strong upregulation of the glial fibrillary acidic protein (GFAP) in astrocytes. Similar alterations are found in transgenic mice expressing the HIV-1 envelope protein gp120 in the CNS. Because alterations of astrocyte functions could contribute to neuronal impairment, we compared brains of gp120 transgenic mice and gp120-transfected C6 astrocytoma cells with controls and found that gp120 induced a prominent elevation of steady state GFAP mRNA levels, …

The prognostic implications of histologic classification and bromodeoxyuridine labeling index of mixed gliomas.

To clarify the biological and clinical behavior and prognosis of mixed gliomas, 47 patients underwent intraoperative bromodeoxyuridine (BrdU) labeling studies. The mean age was 27.8 years at symptom onset and 31.8 years at labeling (median, 36 years). Forty-five tumors were supratentorial, 30 were frontal, and two were cerebellar; 16 were recurrent at labeling. The median labeling index (LI) was 1% (range, < 1 to 15.1%). Forty-six tumors has oligodendroglial and astrocytic elements, and one had astrocytic and ependymal elements. The median LI was 4.4% in recurrent tumors and < 1% in primary tu

Prominent white matter cavitation in an infant with Alexander's disease.

The clinical history and autopsy findings are reported on a case of infantile Alexander's disease (AD). The patient, a white baby girl, deve … y the CNS showed classic features of AD with diffuse paucity of myelin and massive proliferation of astrocytes bearing Rosenthal fibers (RF). The latter appeared as granular osmiophilic deposits associated with 8-10 nm filaments within astrocytic processes and cell bodies by EM. This case of AD is remarkable for the extreme degree of cavitation. Cavitary cha …

Structure, expression, and function of Ng-CAM, a member of the immunoglobulin superfamily involved in neuron-neuron and neuron-glia adhesion.

The neuron-glia cell adhesion molecule (Ng-CAM) mediates neuron-neuron adhesion by a homophilic mechanism and neuron-astrocyte adhesion by a heterophilic mechanism. The protein is expressed on neurons and Schwann cells but not on astrocytes. It is most prevalent during development on cell bodies of migrating neurons and on axons during formation of nerves. Ng-CAM expression is greatly increased following nerve injury. Anti-Ng-CAM antibodies inhibited migration of granule cells along Bergmann glia in cerebellar explants and fasciculation of neurites in outgrowths from explants of dorsal root ga…

The glial reaction in the course of axon regeneration: a stereological study of the rat hypoglossal nucleus.

Both hypoglossal nuclei were examined by electron microscope stereology after unilateral axotomy. The principal aim of this study was a quan … sses, the presumed microglial component was minimal. This study indicates a two-step involvement of astrocytes in regenerative repair. Namely, the first phase seems to result in an increase of lamellar processes through reshaping of the stem process.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme specificity and effects of gyroxin, a serine protease from the venom of the South American rattlesnake Crotalus durissus terrificus, on protease-activated receptors.

Gyroxin is a serine protease displaying a thrombin-like activity found in the venom of the South American rattlesnake Crotalus durissus terr … functional studies of the effects of gyroxin on PARs were conducted in living cells using cultured astrocytes, which express all PARs. Despite the ability to cleavage the PAR-1, -2, -3, and -4 peptides, gyroxin was unable to activate the PARs expressed in astrocytes as determined by evaluating the cytosolic calcium mobilization. On the other hand, we also s …

Associations between plasma biomarker levels and quantitative postmortem neuropathologic measures in Alzheimer's disease and related dementias.

INTRODUCTION: Validation of Alzheimer's disease blood-based biomarkers (BBMs) has relied largely on amyloid beta (Aβ) and tau positron emiss … th postmortem quantitative measures of Aβ plaques, AT8+ pTau neurons, cortical thickness, and GFAP+ astrocytes across the temporal, frontal, and occipital lobes. RESULTS: Plasma p-tau217 strongly associated with Aβ plaques (especially neuritic) and AT8+ neurons. Associations were weaker for p-tau181 and t-tau. NfL associated only with lower cortical thickne …

Neuronal EphB2 signaling drives persistent neuropathic pain following spinal cord injury.

Neuropathic pain after spinal cord injury reflects persistent hyperexcitability in the spinal cord dorsal horn, yet the molecular drivers su … sion within dorsal horn. Although EphB2 transcript levels increased in both dorsal horn neurons and astrocytes, conditional deletion of EphB2 only in dorsal horn neurons, but not in astrocytes, reversed established mechanical allodynia and reduced dorsal horn neuronal activation. These findings identify EphB signaling, and neuronal EphB2 in particular, as a …

HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND.

PURPOSE OF REVIEW: HIV-1-associated neurocognitive disorders (HAND) manifest in 15% to 50% of people with HIV, impairing learning and memory and executive function. The chronic generation of HIV-1 Transactivator of transcription (Tat) likely contributes to HAND via direct neuronal toxicity and glial-mediated toxicity. This review summarizes our current understanding of how chronic Tat generation from microglia and astrocytes promote glutamate excitotoxicity. RECENT FINDINGS: In recent years, the indirect effects of Tat through the activation of glial cells have gained significant interest. Th…

Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies.

Parkinson's disease (PD) is a prevalent age-related neurodegenerative disorder marked by the progressive loss of dopaminergic neurons and the formation of Lewy bodies. Traditionally viewed as primarily a dopaminergic disorder, recent research has highlighted the significant role of neuroinflammation and the complex interplay between glial cells, particularly astrocytes and microglia, in PD pathogenesis. This review explores the multifaceted roles of astrocytes, microglia and oligodendrocytes in PD, focusing on their involvement in maintaining glutamate and ion homeostasis, energy metabolism, a…

C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.

Microglia and neuroinflammation are involved in amyotrophic lateral sclerosis (ALS), but the precise underlying molecular mechanisms remain … pluripotent stem cell (iPSC)-derived microglia. We also found a diminished response of C9orf72 HRE astrocytes and provided a map of dysregulated ligand-receptor pairs in microglia and astrocytes. Our data highlight variations in the cellular substrate of sporadic and inherited forms of ALS, which have implications for patient stratification and selection of …

Neuroglia in Tourette syndrome and obsessive-compulsive disorder.

In recent years, neuroglia have drawn the attention of researchers in the fields of neurology and psychiatry. Besides their well-known functions providing support to neurons, myelinating axons, and clearing up debris, a constantly growing of evidence indicates that glial cells are key contributors to the pathophysiology of neuropsychiatric disorders. Alterations in microglia, astrocytes, and oligodendrocytes have been described in Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). The sudden onset of tics and OCD-like symptoms after infection in children (Pediatric Autoimmune Neur…

Взаимодействие между нейтрофилами и элементами барьера крови и мозга в контексте множественного склероза и ишемического разрушения.

Барьер мозга крови (BBB) представляет собой полупроницаемую мембрану в физиологических условиях, но в патологии, такой, как множественный склероз (MS) и ишемический инсульт (IS), его проницаемость возрастает. В этом обзоре основное внимание уделяется нейтрофильам и их взаимодействию с клеточными компонентами ББД: эндотелиальными клетками (ЭК), перицитами (ПХ) и астроцитами (АК). В настоящее время нейтрофилы получают больше внимания, главным образом благодаря передовым методам исследований, которые показывают сложность их населения. Кроме того, нейтрофилы способны засекать внеклеточные везикли

Совпадение в аннотации оригинала
The blood-brain barrier (BBB) is a semi-permeable membrane in physiological conditions, but in pathologies like multiple sclerosis (MS) and ischemic stroke (IS), its permeability increases. In this review, we focus on neutrophils and their interaction with cellular components of the BBB: endothelial cells (EC), pericytes (PC), and astrocytes (AC). Nowadays, …

ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism.

IP3 receptor (IP3R)-mediated Ca2+ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca2+ up … er and mitochondrial oxidative metabolism due to enrichment of IP3R at MERCS. In human iPSC-derived astrocytes from PD patients, 20 nm MERCS were specifically reduced, which correlated with a reduction of mitochondrial Ca2+ uptake. Stabilization of the ER-mitochondrial interaction at 20 nm, but not at 10 nm, fully rescued mitochondrial Ca2+ uptake in PD astr …

Transcriptomic and metabolic signatures of neural cells cultured under a physiologic-like environment.

Cultured brain cells are used conventionally to investigate fundamental neurobiology and identify therapeutic targets against neural diseases. However, standard culture conditions do not simulate the natural cell microenvironment, thus hampering in vivo translational insight. Major weaknesses include atmospheric (21%) O2 tension and lack of intercellular communication, the two factors likely impacting metabolism and signaling. Here, we addressed this issue in mouse neurons and astrocytes in primary culture. We found that the signs of cellular and mitochondrial integrity were optimal when these…

Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.

In vitro models of the human blood-brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating dis … ls and pericytes as well as physiological shear stresses (~10-20 dyne cm-2) are necessary, and when astrocytes are added, astrocytes or pericytes should outnumber endothelial cells. We expect this meta-analysis to facilitate the design of increasingly physiological models of the BBB.

Parkinson's Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology.

BACKGROUND: The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinso … ation without Lewy bodies or Lewy neurites, but there were frequent tau-immunopositive neurites and astrocytes in the putamen and substantia nigra, neocortical glial tau positive astrocytes associated with aging-related tau astrogliopathy (ARTAG), as well as neurofibrillary tangles, beta amyloid plaques, and amyloid angiopathy typical of advanced Alzheimer's …