Meningeal B Cell Clusters Correlate with Submeningeal Pathology in a Natural Model of Multiple Sclerosis.

Multiple sclerosis (MS) is an idiopathic demyelinating disease in which meningeal inflammation correlates with accelerated disease progression. The study of meningeal inflammation in MS has been limited because of constrained access to MS brain/spinal cord specimens and the lack of experimental models recapitulating progressive MS. Unlike induced models, a spontaneously occurring model would offer a unique opportunity to understand MS immunopathogenesis and provide a compelling framework for translational research.

Eosinophilic Polymyositis: A Rare Cause of Atraumatic Compartment Syndrome of the Forearm.

 Eosinophilic polymyositis is a rare disorder in which eosinophils infiltrate muscle and supporting connective tissue structures, resembling autoimmune or immunologically mediated disease. This disorder can be associated with muscle inflammation and death, and can be a cause of atraumatic compartment syndrome.  This is a retrospective chart review of a case report as well as review of pertinent literature.

Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain.

Inter-alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain.

Ovariectomy Influences Cognition and Markers of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most devastating and costly diseases, and prevalence of AD increases with age. Furthermore, females are twice as likely to suffer from AD compared to males. The cessation of reproductive steroid hormone production during menopause is hypothesized to cause this difference.

Evaluation of the Structure of Myodural Bridges in an Equine Model of Ehlers-Danlos Syndromes.

Myodural bridges have been described in various species as connective tissue structures "bridging" small cranio-cervical muscles to the dura. Myodural bridges are thought to stabilize the dural sac during head and neck movements and promote cerebrospinal fluid motion; however, their role in neurological diseases has not yet been established. We report ultrasonographic visualization, necropsy, histopathologic and ultrastructural findings of myodural bridges in horses with hereditary equine regional dermal asthenia (HERDA), an equine model of Ehlers-Danlos syndromes.

Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats.

Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in the perinatal period. Hypothermia is the only approved intervention for neonatal HI encephalopathy. However, this treatment is only partially protective, has a narrow therapeutic time window after birth and only can be used to treat full-term infants.

Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer's disease.

Background: The roles of the choroid plexus (CP) and cerebrospinal fluid (CSF) production have drawn increasing attention in Alzheimer's disease (AD) research. Specifically, studies document markedly decreased CSF production and turnover in moderate-to-severe AD. Moreover, reduced CP function and CSF turnover lead to impaired clearance of toxic metabolites, likely promote neuroinflammation, and may facilitate neuronal death during AD progression.

Gastrointestinal iron excretion and reversal of iron excess in a mouse model of inherited iron excess.

The current paradigm in the field of mammalian iron biology states that body iron levels are determined by dietary iron absorption, not by iron excretion. Iron absorption is a highly regulated process influenced by iron levels and other factors. Iron excretion is believed to occur at a basal rate irrespective of iron levels and is associated with processes such as turnover of intestinal epithelium, blood loss, and exfoliation of dead skin.

High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats.

Inflammation contributes to neonatal brain injury. Pro-inflammatory cytokines represent key inflammatory meditators in neonatal hypoxic-ischemic (HI) brain injury. The high mobility group box-1 (HMGB1) protein is a nuclear protein with pro-inflammatory cytokine properties when it is translocated from the nucleus and released extracellularly after stroke in adult rodents.

Blood-Cerebrospinal Fluid Barrier Gradients in Mild Cognitive Impairment and Alzheimer's Disease: Relationship to Inflammatory Cytokines and Chemokines.

The pathophysiology underlying altered blood-cerebrospinal fluid barrier (BCSFB) function in Alzheimer's disease (AD) is unknown but may relate to endothelial cell activation and cytokine mediated inflammation. Cerebrospinal fluid (CSF) and peripheral blood were concurrently collected from cognitively healthy controls ( = 21) and patients with mild cognitive impairment (MCI) ( = 8) or AD ( = 11). The paired serum and CSF samples were assayed for a panel of cytokines, chemokines, and related trophic factors using multiplex ELISAs.

Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.

Background: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.

Methods: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP.

Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques.

Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself.

Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer's disease.

Transgenic rat models of Alzheimer's disease were used to examine differences in memory and brain histology. Double transgenic female rats (APP+PS1) over-expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and single transgenic rats (APP21) over-expressing human APP were compared with wild type Fischer rats (WT). The Barnes maze assessed learning and memory and showed that both APP21 and APP+PS1 rats made significantly more errors than the WT rats during the acquisition phase, signifying slower learning.

Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death.

Enteric Pathologic Manifestations of Alpha-Synucleinopathies.

Background: Gastrointestinal (GI) symptoms are common in Parkinson disease (PD), often preceding neurological manifestations; however, early diagnostic utility of GI biopsies remains controversial. Studies suggest aberrant deposition of alpha-synuclein (α-syn) follows step-wise progression in central nervous system though histologic interpretation of normal and aberrant staining patterns have shown variable results. This study examines whether GI α-syn mRNA expression combined with standard α-syn immunohistochemical staining enhance the role of GI biopsy in PD.

Systemic infusions of anti-interleukin-1β neutralizing antibodies reduce short-term brain injury after cerebral ischemia in the ovine fetus.

Perinatal hypoxic-ischemic reperfusion (I/R)-related brain injury is a leading cause of neurologic morbidity and life-long disability in children. Infants exposed to I/R brain injury develop long-term cognitive and behavioral deficits, placing a large burden on parents and society. Therapeutic strategies are currently not available for infants with I/R brain damage, except for hypothermia, which can only be used in full term infants with hypoxic-ischemic encephalopathy (HIE).

The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.

Expression of the orphan C2orf40 gene is associated with the aggregation of the neurofibrillary tangle-protein tau in transgenic mice, tumor suppression, the induction of senescence in CNS, and the activation of microglia and peripheral mononuclear leukocytes. This gene also encodes several secreted pro- and anti-inflammatory neuropeptide-like cytokines, suggesting they might be implicated in the inflammatory component(s) of Alzheimer's disease (AD). Accordingly, we evaluated human AD and control brains for expression changes by RT-qPCR, Western blot, and histological changes by immunolabeling.

Succinate Dehydrogenase B (SDHB) Immunohistochemistry for the Evaluation of Muscle Biopsies.

Succinate dehydrogenase (SDH) is a key mitochondrial enzyme complex composed of 4 subunits. SDH histochemistry is routinely utilized in the assessment of muscle biopsies to reveal underlying pathology such as subsarcolemmal mitochondrial aggregates. In this study, we evaluated the utility of succinate dehydrogenase B (SDHB) immunohistochemistry (IHC) in 27 muscle biopsies, including 13 mitochondrial myopathies (MMs), 9 inflammatory myopathies, and 5 controls.

Atrophy of the tongue following complete versus partial hypoglossal nerve transection in a canine model.

Objectives/hypothesis: The hypoglossal nerve (XII) has been used as a donor nerve in facial and laryngeal reinnervation. The purpose of this study was to investigate the neuromuscular changes that occur within the tongue following partial or complete transection of XII using a canine model.

Study Design: Histopathological comparison of tongue denervation following two types of XII resection in a canine model.

HMGB1 Translocation After Ischemia in the Ovine Fetal Brain.

Inflammation contributes to the evolution of hypoxic-ischemic (HI) brain injury. High-mobility group box-1 (HMGB1) is a nuclear protein that is translocated from the nucleus and released after ischemia in adult rodents and thereby initiates inflammatory responses. However, there is very little information regarding the effects of HI on HMGB1 in immature brains.

P-glycoprotein expression and amyloid accumulation in human aging and Alzheimer's disease: preliminary observations.

P-glycoprotein (P-gp), part of the blood-brain barrier, limits drug access to the brain and is the target for therapies designed to improve drug penetration. P-gp also extrudes brain amyloid-beta (Aβ). Accumulation of Aβ is a hallmark of Alzheimer's disease (AD).

Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus.

The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy.