Identification of central nervous system injury is a critical part of perinatal autopsies; however, injury is not always easily identifiable due to autolysis and immaturity of the developing brain. ...Here, the role of immunohistochemical stains in the identification of perinatal brain injury was investigated. Blinded semiquantitative scoring of injury was performed on sections of frontal lobe from 76 cases (51 liveborn and 25 stillborn) using H&E, GFAP, Iba-1, and β-APP stains. Digital image analysis was used to quantify GFAP and Iba-1 staining. Commonly observed pathologies included diffuse white matter gliosis (DWMG) and white matter necrosis (WMN). DWMG scores were very similar on H&E and GFAP stains for liveborn subjects. For stillborn subjects, DWMG scores were significantly higher on GFAP stain than H&E. β-APP was needed for identification of WMN in 71.4% of stillborn subjects compared to 15.4% of liveborn subjects. Diffuse staining for Iba-1 within cortex and white matter was positively correlated with subject age. Staining quantification on digital image analysis was highly correlated to semiquantitative scoring. Overall, GFAP and β-APP stains were most helpful in identifying white matter injury not seen on H&E in stillborn subjects. Immunostains may therefore be warranted as an integral part of stillborn brain autopsies.
In injury and disease, microglia and astrocytes - two major non-neuronal cell types in the central nervous system (CNS) - undergo morphological, transcriptional, and functional changes, which can ...underlie pathogenesis and dysfunction of the CNS. Microglia, the brain's tissue resident parenchymal macrophages, are described as becoming “activated” as they deftly change their production of different inflammatory mediators, alter the surveillance behavior of their cellular protrusions, and differentially influence the function of astrocytes. For their part, astrocytes – the most abundant glial cell type – are said to become “reactive”, which implies (perhaps inappropriately) causality for the changes astrocytes undergo. Reactive astrocytes variably undergo process hypertrophy, decrease their normal homeostatic functions such as facilitating synapse formation, and in some cases act to form a tissue scar in response to insult. But what do these terms “activation” and “reactivity” mean, anyway? And how do these changed microglia and astrocytes contribute to neurodegenerative disease (ND)? Here, we describe our current understanding of the role of activated and reactive microglia and astrocytes in ND, as well as our current understanding about what these states are and might mean. We survey the earliest description of these cells by histopathologists, their transcriptomic identities, and finally our mechanistic understanding of their functions in ND.
Abstract
Germ cell tumours of the central nervous system and tumours of the sellar region represent a diverse group of neoplasms. These tumours affect both paediatric and adult patients and represent ...some of the most common central nervous system tumours as well as rare entities. Diagnosis frequently relies on tissue sampling, and intraoperative consultation is often needed to guide surgical management. The focus of this article is to provide a reference for the intraoperative cytology of these entities. The cytological features of these tumours as well as their differential diagnoses are described.
Germ cell tumours and tumours of the sellar region represent a diverse group of neoplasms. The intraoperative cytology of these entities as well as their differential diagnoses are discussed.
Molecular diagnostics have dramatically influenced the classification of tumor groups in the 2021 WHO CNS tumor classification. Studies focusing on molecular diagnostics continue to identify new ...tumors. Soon after the summary of the new classification was published, “Supratentorial Neuroepithelial Tumor with PLAGL1 Fusion” was described as a distinct entity. Although this new entity is defined pathologically, its imaging features are undefined. This case report discusses the imaging findings and possible differential diagnosis of the new tumor.
The classification of tumors of the central nervous system (CNS) is a rapidly evolving field. While tumors were historically classified on the basis of morphology, the recent integration of molecular ...information has greatly refined this process. In some instances, molecular alterations provide significant prognostic implications beyond what can be ascertained by morphologic examination alone. Additionally, tumors may harbor molecular alterations that provide a therapeutic target. Pediatric CNS tumors, in particular, rely heavily on the integration of molecular data with histologic, clinical, and radiographic features to reach the most accurate diagnosis. This review aims to provide insight into a neuropathologist's approach to the clinical workup of pediatric brain tumors with an ultimate goal of reaching an integrated diagnosis that provides the most accurate classification and informs prognosis and therapy selection. The primary focus will center on how histology and molecular findings are used in combination with clinical and radiographic information to reach a final, integrated diagnosis.
Abstract
Ribbon effect describes a perceived macroscopic color reversal of the gray and white matter, characterized by a pale cortex and diffusely dusky underlying white matter. This finding is ...thought to be unique to the perinatal period and indicative of hypoxic-ischemic injury. However, the clinical and microscopic correlates of this macroscopic finding have not been clearly defined. A 21-year retrospective study of autopsies was performed. Ribbon effect was seen in 190 subjects, ages 20 weeks gestation to 9.5 months adjusted age. Clinical associations and radiographic findings were similar in ribbon effect cases and controls. A variety of histologic findings were observed including acute neuronal injury, diffuse white matter gliosis, and white matter necrosis. Only white matter vascular congestion was significantly correlated to the macroscopic severity of ribbon effect; the severity of white matter injury and acute neuronal injury were not significantly correlated to ribbon effect. While hypoxic-ischemic changes were present in nearly all cases of ribbon effect, the location, severity, and chronicity of these changes varied considerably, and similar findings were observed in controls. The presence of ribbon effect therefore does not predict microscopic findings apart from vascular congestion, highlighting the importance of microscopic examination in perinatal brain autopsies.
Ependymomas (EPN) are commonly encountered brain tumors in the pediatric population. They may arise in the supratentorial compartment, posterior fossa and spinal cord. Histopathologic grading of EPN ...has always been challenging with poor interobserver reproducibility and lack of correlation between histologic grade and patient outcomes. Recent studies have highlighted that, despite histopathological similarities among variants of EPN at different anatomical sites, they possess site-specific genetic and epigenetic alterations, transcriptional profiles and DNA copy number variations. This has led to a molecular and location-based classification for EPN which has been adopted by the World Health Organization Classification of Central Nervous System Tumors and more accurately risk-stratifies patients than histopathologic grading alone. Given the complexity of this evolving field, the purpose of this paper is to offer a practical approach to the diagnosis of EPN, including the selection of the most appropriate molecular surrogate immunohistochemical stains, basic molecular studies and more sophisticated techniques if needed. The goal is to reach a rapid, sound diagnosis, providing essential information regarding prognosis and guiding clinical decision-making.
Primary somatosensory cortex (S1) receives two distinct classes of thalamocortical input via the lemniscal and paralemniscal pathways, the former via ventral posterior medial nucleus (VPM), and the ...latter, from the posterior medial nucleus (POm). These projections have been described as parallel thalamocortical pathways. Although the VPM thalamocortical projection has been studied in depth, several details of the POm projection to S1 are unknown. We studied the synaptic properties and anatomical features in the mouse of the projection from POm to all layers of S1 and to layer 4 of secondary somatosensory cortex (S2). Neurons in S1 responded to stimulation of POm with what has been termed Class 2 properties (paired-pulse facilitation, small initial excitatory postsynaptic potentials (EPSPs), a graded activation profile, and a metabotropic receptor component; thought to be modulatory), whereas neurons in layer 4 of S2 responded with Class 1A properties (paired-pulse depression, large initial EPSPs, an all-or-none activation profile, and no metabotropic receptor component, thought to be a main information input). Also, labeling from POm produced small boutons in S1, whereas both small and large boutons were found in S2. Our data suggest that the lemniscal and paralemniscal projections should not be thought of as parallel information pathways to S1 and that the paralemniscal projection may instead provide modulatory inputs to S1.
Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents
and are dysregulated in multiple human neurological ...disorders
. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate
. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice
. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.
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