ABSTRACT
Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte-neuron lactate shuttle (ANLS) and the glutamate-glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1ß signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1ß and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others, MS NAGM astrocytes express inflammasome components and that astrocytes are capable to release Il-1ß in-vitro. Altogether, our data suggests that immune signaling of immune- and/or central nervous system origin drives alterations in astrocytic ANLS and GGC gene regulation in the MS NAGM. Such a mechanism might underlie cortical brain dysfunctions frequently encountered in MS patients.
Subject(s)
Astrocytes/immunology , Cerebral Cortex/immunology , Gene Expression , Multiple Sclerosis/genetics , Signal Transduction/genetics , Adult , Aged , Aged, 80 and over , Animals , Astrocytes/metabolism , Astrocytes/pathology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Female , Humans , Male , Mice , Middle Aged , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Neurons/immunology , Neurons/metabolism , Neurons/pathology , Signal Transduction/immunology , Young AdultSubject(s)
Calcium Hydroxide/therapeutic use , Gutta-Percha/adverse effects , Root Canal Filling Materials/therapeutic use , Root Canal Obturation/adverse effects , Tooth Apex/drug effects , Adolescent , Calcification, Physiologic/drug effects , Female , Foreign Bodies/etiology , Humans , Incisor/injuries , Periapical Tissue , Retreatment , Root Canal Filling Materials/adverse effects , Tooth Apex/physiopathology , Tooth Bleaching , Tooth Discoloration/therapyABSTRACT
Intracoronal radiolucencies in unerupted teeth are an uncommon radiographic finding; but their early detection and classification allow the most appropriate management protocol to be developed. Early separation of lesions into those that are developmental and remain static and those that are reactive and aggressive is necessary for a controlled outcome. The current paper reviews possible formative mechanisms and describes a case of severe intracoronal resorption resulting in loss of the tooth.
Subject(s)
Tooth Crown/diagnostic imaging , Tooth Resorption/diagnostic imaging , Tooth, Unerupted/diagnostic imaging , Child , Dental Enamel/diagnostic imaging , Dental Enamel/pathology , Dentin/pathology , Female , Humans , Radiography , Tooth Crown/pathology , Tooth Eruption , Tooth Extraction , Tooth Loss/etiology , Tooth Resorption/classification , Tooth Resorption/pathology , Tooth Resorption/surgery , Treatment OutcomeABSTRACT
The purpose of this study was to investigate the incidence of pulpal floor damage caused by operator error in a standard pulpotomy exercise, and to determine if this damage produced significant changes in dentin morphology and thickness at the base of the pulp chamber. One hundred and fourteen primary molar teeth were utilized in this study, 61 having pulpotomies and the remainder untreated. The dentin thickness in the furcation was measured on all the teeth and the pulpal floor morphology was examined using both light and scanning electron microscopy. The difference in thickness of dentin in the furcation of pulpotomized and non-pulpotomized teeth was not statistically significant. Less than fourteen per cent of pulpotomized teeth showed damage to the pulpal floor and this damage was only minimal in all cases. This study therefore suggests that damage to the pulpal floor during preparation is unlikely to be a factor contributing to failure of pulpotomies.