neuropathology cytopathology

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting in early childhood. The neuropathological hallmarks of the disease - cortical tubers, containing cytopathological neuronal and glial cell types - appear to be the source of seizure initiation. However, the contribution of these aberrant cell populations to TSC-associated epilepsies is not fully understood. To gain further insight, investigators have attempted to generate animal models with TSC-like brain abnormalities...

INTRODUCTION: Malformations of the cerebral cortex are a frequent cause of pharmacoresistant epilepsies and developmental disorders. EPIDEMIOLOGY AND GENETICS: The incidence of cortical dysplasias in epilepsy surgical series varies from 12 to 40% and focal cortical dysplasias (FCD) are one of the most common neuropathological findings in resection specimens from pediatric patients undergoing cortical resections for the treatment of refractory epilepsy. MACROSCOPY AND HISTOPATHOLOGY: Surgical specimens in FCD may appear normal macroscopically, but in some cases, widening of the cortex with poor demarcation from the underlying white matter is noted...

Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical cholinergic projections are prominent components of the neuropathology in Alzheimer's disease (AD). The AD brain is also associated with a degeneration of the noradrenergic projections arising from the nucleus locus coeruleus (LC), but the time course of this lesion is poorly understood. To determine whether the LC displays neurofibrillary abnormalities early in the course of events leading to AD, we examined tissue specimens from seven cognitively normal controls and five subjects at the stages of mild cognitively impairment (MCI) or early AD...

The overall impact of prion disease on gene expression is not well characterized. We have carried out a large-scale expression analysis of specific cell types commonly employed in studies of prion disease. Neuroblastoma cells (N2a) and hypothalamic neuronal cells (GT1) can be persistently infected with mouse-adapted scrapie prions, the latter demonstrating cytopathologic effects associated with prion neuropathology. Exploiting a mouse DNA microarray containing approximately 21,000 spotted cDNAs, we have identified several hundred differentially expressed sequences in the two cell lines when infected with prion strain RML...

The cytoskeleton plays a key role in maintaining the highly asymmetrical shape and structural polarity of neurons that are essential for neuronal physiology. Cytoskeletal reorganization plays a key role in neuritogenesis. In neurodegenerative diseases, the cytoskeleton is abnormally assembled and impairment of neurotransmission occurs. In Alzheimer's disease, abundant amyloid plaques and neurofibrillary tangles constitute the two major neuropathologic alterations present in the brain. Neurofibrillary tangles are formed of paired helical filaments consisting nearly entirely of the microtubule-associated protein tau...

Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in the disease. Indeed, that oxidative mechanisms are involved in the cell loss and other neuropathology associated with AD is evidenced by the large number of metabolic signs of oxidative stress as well as by markers of oxidative damage. However, what is intriguing is that oxidative damage decreases with disease progression, such that levels of markers of rapidly formed oxidative damage, which are initially elevated, decrease as the disease progresses to advanced AD...

Hereditary spastic paraparesis (HSP) is a genetically heterogeneous disorder, the most common cause of which is mutation of the spastin gene. Recent evidence suggests a role for spastin in microtubule dynamics, but the distribution of the protein within the CNS is unknown. The core neuropathology of HSP is distal degeneration of the lateral corticospinal tract and of fasciculus gracilis, but there are few neuropathological studies of cases with a defined mutation. We aimed to determine the distribution of spastin expression in the human CNS and to investigate the cellular pathology of the motor system in HSP due to mutation of the spastin gene...

Glutamate (glu) is a major excitatory transmitter and a toxin in the brain. In the present study, the immature rat hippocampal slice was used to determine the morphology, topography, ionic mediation and receptor specificity of glu toxicity. Slices were exposed to glu for 30 min, and the damage was evaluated after 3 h of recovery in regular medium. The effects on glu toxicity of changes of [Ca2+], [Cl-] and [Na+] were determined. The receptor preference of glu was assessed by using the N-methyl-D-aspartate (NMDA) antagonist MK-801 and the kainate (KA)/quisqualate (QA) antagonist DNQX, alone or in combination...

Neuropathological effects of the pesticides paraquat (PQ, a herbicide) and triphenyltin (TPT, a fungicide) were studied on the postclitellar segmental ganglia of juvenile E. fetida specimens using light and electron microscopic methods. Growth retardation of the worms in standard culture medium was used as quantitative marker of sublethal effect. There is a distinct neuron group in the segmental ganglia characterised by high sensitivity against PQ- and another one against TPT-toxication. However the marked histo- and neurocytopathological alterations were similar in PQ and TPT treated worms...

The FVB mouse is used extensively in transgenic research because of its defined inbred background, superior reproductive performance, and prominent pronuclei, which facilitate microinjection of genomic material. Seizures associated with a known mutation and seizure-susceptible inbred strains are well documented in mice; however, to the authors' knowledge, seizures in the FVB strain have not been evaluated. Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice generated, using eight unrelated transgenic constructs (n = 63), were submitted for pathologic examination...

This article reviews the cytoskeletal abnormalities, morphologic lesion patterns, and resulting pathophysiology of the most frequent neurodegenerative movement disorders caused by dysfunction of the basal ganglia and related neuronal loops. The following topics are discussed: Among the akinetic-rigid Lewy body disorders is idiopathic Parkinson's disease, which reveals specific lesion patterns of pathophysiologic and therapeutic relevance. Dementia with Lewy bodies characterized by cortical Lewy bodies appears intermediate between Parkinson's and Alzheimer's diseases...

Neuronal death and vacuolation are characteristics of the CNS degeneration found in prion diseases. Relatively few cultured cell lines have been identified that can be persistently infected with scrapie prions, and none of these cells show cytopathologic changes reminiscent of prion neuropathology. The differentiated neuronal cell line GT1, established from gonadotropin hormone releasing-hormone neurons immortalized by genetically targeted tumorigenesis in transgenic mice (P. L. Mellon, JJ. Windle, P. C. Goldsmith, C...

Human cytomegalovirus (HCMV) can frequently infect the central nervous system (CNS) in the setting of immunosuppression such as transplantation and infection with the human immunodeficiency virus (HIV). Our laboratory previously reported that HCMV infection of human brain aggregates preferentially infected a microglial/macrophage (M/M) and caused a neuropathology that differed between strains and could occur in the absence of antigen expression. We extended these studies by infecting a human brain cell aggregate model with four low passage clinical isolates of HCMV...

A 57-year-old woman showed progressive sensory aphasia as an initial symptom, and then developed total aphasia within 6 years and, finally, severe dementia. Neuropathologically, the cerebral cortex was most severely affected in the superior and transverse temporal gyri, and subsequently in the inferior frontal gyrus, especially in the pars opercularis. The degeneration in the subcortical grey matter was most severe in the substantia nigra, and it was moderate to mild in the ventral part of thalamus, globus pallidus and striatum...

This report concerns an autopsy case of corticobasal degeneration (CBD). The patient was a 64-year-old woman with slowly progressing clumsiness and gait disturbance who died approximately 7 years after the onset of symptoms. The salient neuropathological findings were focal loss of neurons of the cerebral cortex, ballooned neurons and gliosis of the subcortical white matter, thalamus, and basal ganglia. In addition, there were marked neuronal loss and gliosis in the substantia nigra. The ballooned neurons were positively immunostained for phosphorylated neurofilament, alpha B-crystallin and synaptophysin; staining for the latter was intraneuronal...

Although neuropathological examination is the "gold standard" for the diagnosis of neurodegenerative disorders with extrapyramidal features, difficulties may arise in the morphological differentiation of some of these disorders. They are all associated with major structural pathology within or directly affecting the basal ganglia and related neuronal loops. In addition to progressive neuronal loss and gliosis involving specific subcortico-cortical systems or multiple circuits, many of these disorders are characterized by intracellular neuronal and/or glial inclusions indicating cytoskeletal dysmetabolism that may serve as important diagnostic signposts, whereas in other disorders, e...

Substantial neuronal loss in the superior frontal gyrus in patients who have died of AIDS have been reported previously. This investigation examined the distribution of neuronal loss in three other neocortical areas and, alteration in neuronal volume in four neocortical areas. This was carried out using two stereological probes, the "disector" and the "nucleator". These recently developed methods provide estimations, regardless of size and shape, in real three-dimensional space, and are more efficient than conventional quantitation...

The molecular basis of neurologic dysfunction in prion diseases is unknown. Spongiform degeneration of neurons is the most characteristic neuropathologic change which raises the possibility of abnormal ion channel function. Here we examined the regulation of Ca2+ fluxes in two cell lines chronically infected with scrapie prions, designated ScN2a (scrapie-infected mouse neuroblatoma) and ScHaB (scrapie-infected hamster brain) cells. In uninfected HaB cells, bradykinin caused increases in intracellular Ca2+ concentration ([Ca2+]i) by release of Ca2+ from internal stores and influx of extracellular Ca2+ whereas, in N2a cells, bradykinin increased [Ca2+]i exclusively from internal stores...

Clinico-neuropathological findings recorded from one case of cerebral gliomatosis are reported in this paper. Immunocytochemical methods (GFAP, protein S-100) were used together with morphometric computer-assisted analysis for more effective investigation of certain cytopathological features such as the relationship between cerebral gliomatosis and low-graded astrocytoma. Immunohistochemically, most of the proliferating cells were positive to GFAP and/or to protein S-100, which was in fair agreement with publications elsewhere in the literature...

Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent...