ABSTRACT
Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Subject(s)
Mice , Animals , Gliosis/pathology , Cicatrix/pathology , Spinal Cord Injuries , Astrocytes/metabolism , Spinal Cord/pathology , Fibrosis , Mammals , Receptors, G-Protein-CoupledABSTRACT
When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.
Subject(s)
Humans , Astrocytes , Axons/pathology , Cicatrix/pathology , Gliosis/pathology , Medicine, Chinese Traditional , Nerve Regeneration , Stroke/drug therapyABSTRACT
Abstract Purpose: Spinal Cord injury represents, in veterinary medicine, most of the neurological attendances and may result in permanent disability, death or euthanasia. Due to inflammation resulting from trauma, it originates the glial scar, which is a cell interaction complex system. Its function is to preserve the healthy circuits, however, it creates a physical and molecular barrier that prevents cell migration and restricts the neuroregeneration ability. Methods: This review aims to present innovations in the scene of treatment of spinal cord injury, approaching cell therapy, administration of enzyme, anti-inflammatory, and other active principles capable of modulating the inflammatory response, resulting in glial scar reduction and subsequent functional improvement of animals. Results: Some innovative therapies as cell therapy, administration of enzymes, immunosuppressant or other drugs cause the modulation of inflammatory response proved to be a promising tool for the reduction of gliosis. Conclusion: Those tools promise to reduce gliosis and promote locomotor recovery in animals with spinal cord injury.
Subject(s)
Animals , Rats , Spinal Cord Injuries/therapy , Cicatrix/veterinary , Gliosis/veterinary , Stem Cells , Veterinary Medicine , Cicatrix/pathology , Recovery of Function , Disease Models, Animal , Gliosis/etiology , Gliosis/pathologyABSTRACT
Epilepsy is a disease with serious consequences for patients and society. In many cases seizures are sufficiently disabling to justify surgical evaluation. In this context, Magnetic Resonance Imaging (MRI) is one of the most valuable tools for the preoperative localization of epileptogenic foci. Because these lesions show a large variety of presentations (including subtle imaging characteristics), their analysis requires careful and systematic interpretation of MRI data. Several studies have shown that 3 Tesla (T) MRI provides a better image quality than 1.5 T MRI regarding the detection and characterization of structural lesions, indicating that high-field-strength imaging should be considered for patients with intractable epilepsy who might benefit from surgery. Likewise, advanced MRI postprocessing and quantitative analysis techniques such as thickness and volume measurements of cortical gray matter have emerged and in the near future, these techniques will routinely enable more precise evaluations of such patients. Finally, the familiarity with radiologic findings of the potential epileptogenic substrates in association with combined use of higher field strengths (3 T, 7 T, and greater) and new quantitative analytical post-processing techniques will lead to improvements regarding the clinical imaging of these patients. We present a pictorial review of the major pathologies related to partial epilepsy, highlighting the key findings of 3 T MRI.
Subject(s)
Humans , Epilepsies, Partial/diagnosis , Magnetic Resonance Imaging/methods , Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Central Nervous System Vascular Malformations/diagnosis , Central Nervous System Vascular Malformations/pathology , Epilepsies, Partial/pathology , Gliosis/diagnosis , Gliosis/pathology , Malformations of Cortical Development/diagnosis , Malformations of Cortical Development/pathology , Sclerosis , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/pathologyABSTRACT
OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes.
Subject(s)
Animals , Male , Rabbits , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Gliosis/pathology , Retina/drug effects , Retinal Ganglion Cells/drug effects , Cell Death/drug effects , Gliosis/chemically induced , Intravitreal Injections , Models, Animal , Random Allocation , Retina/growth & development , Retinal Ganglion Cells/pathology , Statistics, Nonparametric , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
OBJECTIVE: Early brain insults can cause cavitary lesions including porencephaly (POR) and multicystic encephalopathy (MCE). The objective of this study was to investigate clinical and electrographic correlates associated to these types of destructive brain lesions. METHOD: Patients with POR and MCE were selected and submitted to clinical and Video-EEG monitoring. The following variables were analyzed: demographic data, type of lesion, presence of gliosis, perinatal complications, epilepsy, brain atrophy, and presence and frequency of epileptiform discharges. RESULTS: Twenty patients were included, 65 percent males, 35 percent females, ages ranging from 1 to 40 years, 14 with MCE and 6 with POR. Eighteen patients had hemiparesis, 19 had epilepsy (current or in the past), seven of them had refractory seizures, and 16 had epileptiform discharges. All patients with MCE had gliosis while only 2 with POR had it. CONCLUSIONS: No correlation was observed between type of lesion and clinical and electrographical outcome. However, a positive correlation was observed between frequency of discharges and presence of brain atrophy, and between MCE and gliosis.
OBJETIVO: Insultos cerebrais precoces podem causar lesões cavitárias incluindo porencefalias (POR) e encefalomalacias multicisticas (EMC). O objetivo deste estudo foi investigar correlatos clínicos e eletrográficos associados a estes dois tipos de lesões destrutivas. MÉTODO: Pacientes com POR e EMC foram selecionados e submetidos à avaliação neurológica e monitorização vídeo-eletrencefalográfica, analisando-se as seguintes variáveis: dados demográficos, tipo de lesão, presença de gliose, complicações perinatais, epilepsia, atrofia cerebral, presença e freqüência de descargas epilépticas. RESULTADO: Vinte pacientes foram incluídos, sendo 65 por cento do sexo masculino, 35 por cento do feminino, idades entre 1 e 40 anos, sendo 14 com EMC e 6 com POR. Dezoito pacientes tinham hemiparesia, 19 tinham ou tiveram epilepsia (7 deles refratários ao tratamento medicamentoso) e 16 deles tinham paroxismos epileptiformes. Todos com MCE tinham gliose associada, contra apenas 2 dos pacientes com POR. CONCLUSÃO: Não houve correlação entre tipo de lesão e evolução clínica e eletrográfica. Houve, entretando, correlação positiva entre freqüência de descargas epilépticas e presença de atrofia cerebral, e entre lesão do tipo EMC e presença de gliose.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Central Nervous System Cysts/pathology , Cerebral Cortex/pathology , Encephalomalacia/pathology , Atrophy/pathology , Central Nervous System Cysts/complications , Central Nervous System Cysts/physiopathology , Cerebral Cortex/physiopathology , Electroencephalography , Encephalomalacia/complications , Encephalomalacia/physiopathology , Epilepsy/etiology , Epilepsy/pathology , Gliosis/pathology , Magnetic Resonance ImagingABSTRACT
La gliosis masiva retiniana es una proliferación reactiva benigna de la astrología retiniana que asume patrón pseudotumoral. Se puede localizar sectorialmente en la retina, especialmente en la periferia u ocupar toda la cavidad ocular. Esta proliferación glial se asocia a cambios reactivos, reparativos, inflamatorios o proliferativos de otras estructuras oculares que complican el cuadro y dificultan el diagnóstico como son la hiperplasia adenomatoide del epitelio pigmentado y no pigmentado del cuerpo ciliar, la metaplasia ósea y mieloide, etc. El diagnóstico de la histogénesis se alcanza por medio de la histoinmunoquímica y la microscopía electrónica de transmisión
Subject(s)
Humans , Retinal Diseases/pathology , Gliosis/pathology , Immunohistochemistry , Microscopy, ElectronABSTRACT
Analisaram-se retrospectivamente 28 casos com diagnóstico clínico e angiográfico de fibrose pré-macular a fim de detectar os eventos retinianos associados ou intercorrentes. Em 67,8 por cento dos casos, estas situaçöes foram notadas, e em 17,8 por cento teve-se evidência indiscutível de vazamento.
Subject(s)
Humans , Male , Female , Middle Aged , Gliosis , Angiography , Macular Degeneration/etiology , Gliosis/complications , Gliosis/pathology , Retrospective StudiesABSTRACT
En un período de cuatro años se revisan 80 casos de leucocoria, encontrándose dos casos anatomopatológicos de gliosis masiva de retina. Se efectúa estudios de microscopía electrónica y estudio inmunohistoquímico. Los hallazgos demostraron que la masa pseudotumoral se debía a proliferación de células fusiformes de citoplasma eosinofílico fibrilar y que el método de la peroxidasa antiperoxidasa confirmó como tejido glial. La microscopía electrónica demostró un patrón similar al presentado por las células de Muller