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Neuropathological Changes (neuropathological + change)
Selected AbstractsNeuropathological changes in vibration injury: An experimental studyMICROSURGERY, Issue 1 2005Hani S. Matloub M.D. Vibration syndrome, a clinical condition arising from chronic use of vibrating tools, is associated with a spectrum of neurovascular symptoms. To date, only its vascular pathology has been extensively studied; we sought to determine what direct neurologic injury, if any, is caused by vibration. Hindlimbs of anesthetized rats were affixed to a vibrating platform 4 h a day for 7 days. Study animals were vibrated with set parameters for frequency, acceleration, velocity, and amplitude; control animals were not vibrated. On day 7, nerves were studied by light and electron microscopy. While light microscopy showed minimal histologic differences between vibrated (n = 12) and control (n = 12) nerves, electron microscopic changes were dramatic. Splitting of the myelin sheath and axonal damage (e.g., myelin balls and "finger ring") were consistently seen in both myelinated and nonmyelinated axons. Despite relatively short vibration, definite pathology was demonstrated, suggesting that vibration syndrome has a direct neurologic component. © 2005 Wiley-Liss, Inc. Microsurgery 25:71,75, 2005. [source] 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Emmanuel Brouillet Abstract Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the gene encoding Huntingtin. The mechanisms underlying the preferential degeneration of the striatum, the most striking neuropathological change in HD, are unknown. Of those probably involved, mitochondrial defects might play an important role. The behavioural and anatomical similarities found between HD and models using the mitochondrial toxin 3-nitropropionic acid (3NP) in rats and primates support this hypothesis. Here, we discuss the recently identified mechanisms of 3NP-induced striatal degeneration. Two types of important factor have been identified. The first are the ,executioner' components that have direct roles in cell death, such as c-Jun N-terminal kinase and Ca2+ -activated protease calpains. The second are ,environmental' factors, such as glutamate, dopamine and adenosine, which modulate the striatal degeneration induced by 3NP. Interestingly, these recent studies support the hypothesis that 3NP and mutated Huntingtin have certain mechanisms of toxicity in common, suggesting that the use of 3NP might give new insights into the pathogenesis of HD. Research on 3NP provides additional proof that the neurochemical environment of a given neurone can determine its preferential vulnerability in neurodegenerative diseases. [source] Neuropathological correlates to clinically defined dementia with Lewy bodiesINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2001E. Londos Abstract Objectives To analyse the neuropathological changes behind clinically defined dementia with Lewy bodies (clinDLB) compared with clinically diagnosed Alzheimer's disease (clinAD). Methods The prevalence of neuropathological findings in 48 clinDLB and 45 clinAD cases was compared. Sixteen clinDLB and 10 clinAD cases were reassessed with ,-synuclein staining for Lewy bodies (LB). Results Alzheimer pathology was found in 81% of the clinDLB and 93% of the clinAD cases. The clinDLB group had a higher prevalence of frontal white matter pathology, mostly of ischemic type, and a more severe degeneration of the substantia nigra compared with the clinAD group. In hematoxylin,eosin staining, LBs were identified in seven (15%) of the clinDLB and in four (9%) of the clinAD group. In ,-synuclein staining, 38% of the clinDLB and 40% of the clinAD cases exhibited LBs. The cases without LBs, in the clinDLB group, had AD pathology in combination with frontal white matter disease. Vascular pathology of significant degree was prevalent in more than 40% of all the cases with verified LBs regardless of clinical diagnosis. Conclusion Consecutive dementia cases, fulfilling the clinical consensus criteria for DLB, may exhibit combinations of neuropathological changes which in themselves can explain the clinical picture of DLB even when LBs are absent. Copyright © 2001 John Wiley & Sons, Ltd. [source] Anoxia leads to a rapid translocation of human trypsinogen 4 to the plasma membrane of cultured astrocytesJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Krisztián Tárnok J. Neurochem. (2010) 115, 314,324. Abstract Trypsinogen 4 is specifically expressed in the human brain, mainly by astroglial cells. Although its exact role in the nervous tissue is yet unclear, trypsin 4-mediated pathological processes were suggested in Alzheimer's disease, multiple sclerosis and ischemic injury. In the present study, we analyzed the intracellular distribution of fluorescently tagged human trypsinogen 4 isoforms during normal and anoxic conditions in transfected mouse primary astrocytes. Our results show that initiation of anoxic milieu by the combined action of KCN treatment and glucose deprivation rapidly leads to the association of leader peptide containing trypsinogen 4 constructs to the plasma membrane. Using rhodamine 110 bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide), a synthetic chromogen peptide substrate of trypsin, we show that anoxia can promote extracellular activation of trypsinogen 4 indicating that extracellular activation of human trypsinogen 4 can be an important component in neuropathological changes of the injured human brain. [source] Amygdalar and hippocampal MRI volumetric reductions in Parkinson's disease with dementiaMOVEMENT DISORDERS, Issue 5 2005Carme Junqué PhD Abstract Parkinson's disease (PD) involves neuropathological changes in the limbic system that lead to neuronal loss and volumetric reductions of several nuclei. We investigated possible volumetric reductions of the amygdala and hippocampus associated to PD. We carried out magnetic resonance imaging (MRI) volumetric studies in 16 patients with PD and dementia (PDD), 16 patients with PD without dementia (PD), and 16 healthy subjects. The general analysis of variance (ANOVA) showed a significant group effect (for the amygdala, P = 0.01; for the hippocampus, P = 0.005). A post-hoc test demonstrated that the differences were due to PDD and control group comparisons for the amygdala (P = 0.008) and for the hippocampus (P = 0.004). In nondemented PD subjects, we observed an 11% reduction in the amygdala and a 10% reduction in the hippocampus compared with that in controls. In summary, demented PD patients have clear amygdalar and hippocampal atrophy that remains statistically significant after controlling for global cerebral atrophy. Nondemented PD patients also showed a degree of volumetric reduction in these structures although the differences were not statistically significant. © 2005 Movement Disorder Society [source] Does Alzheimer's disease begin in the brainstem?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2009G. Simic Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high-order neocortical areas, whereas noncognitive, behavioural and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake,sleep cycle, confusion, agitation and depression have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak and Braak staging system and National Institutes of Aging , Reagan Institute (NIA-RI) criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, ,-amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes. [source] An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitisPHYTOTHERAPY RESEARCH, Issue 8 2008Azita Parvaneh Tafreshi Abstract Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS14 in EAE mice. EAE mice were fed with MS14 containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS14 -fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS14 fed mice. Copyright © 2008 John Wiley & Sons, Ltd. [source] Amygdala kindling develops without mossy fiber sprouting and hippocampal neuronal degeneration in ratsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2001Mariko Osawa MD Abstract Repeated electrical stimulation of limbic structures has been reported to produce the kindling effect together with morphological changes in the hippocampus such as mossy fiber sprouting and/or neuronal loss. However, to argue against a causal role of these neuropathological changes in the development of kindling-associated seizures, we examined mossy fiber sprouting in amygdala (AM)-kindled rats using Timm histochemical staining, and evaluated the hippocampal neuronal degeneration in AM-kindled rats by terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labelling (TUNEL). Amygdala kindling was established by 10.3 ± 0.7 electrical stimulations, and no increase in Timm granules (neuronal sprouting) was observed up to the time of acquisition of a fully kindled state. However, the density and distribution of Timm granules increased significantly in the dentate gyrus compared with unkindled rats after 29 after-discharges or more than 10 kindled convulsions. In addition, no significant increase in TUNEL-positive cells was found in the hilar polymorphic neurons or in CA3 pyramidal neurons of the kindled rats that had fewer than 29 after-discharges. However, a significant increase of TUNEL-positive cells was found in the granule cell layer in the dentate gyrus of the stimulated side after 18 after-discharges or 10 kindled convulsions. Our result show that AM kindling develops without evidence of mossy fiber sprouting, and that mossy fiber sprouting may appear after repeated kindled convulsions, following death of the granule cells in the dentate gyrus. [source] Human prion strain selection in transgenic mice,ANNALS OF NEUROLOGY, Issue 2 2010Kurt Giles DPhil Objective: Transgenic (Tg) mice expressing chimeras of mouse and human prion proteins (PrPs) have shorter incubation periods for Creutzfeldt-Jakob disease (CJD) prions than mice expressing full-length human PrP. Increasing the sequence similarity of the chimeric PrP to mouse PrP, by reverting human residues to mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic (s) CJD prions in ,110 days. Methods: Mice expressing chimeric mouse/human PrP transgenes were produced. The mice were inoculated intracerebrally with extracts prepared from the brains of patients who died of CJD. Onset of neurological dysfunction marked the end of the incubation time. After sacrifice of the Tg mice, their brains were analyzed for PrPSc and neuropathological changes. Results: Reversion of 1 additional residue (M111V) resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in ,75 days. Tg1014 mice also have shorter incubation periods for variant (v) CJD prions, providing a more tractable model for studying this prion strain. Transmission of vCJD prions to Tg1014 mice resulted in 2 different strains, determined by neuropathology and biochemical analysis, which correlated with the length of the incubation time. One strain had the biochemical, neuropathological, and transmission characteristics, including longer incubation times, of the inoculated vCJD strain; the second strain produced a phenotype resembling that of sCJD prions including relatively shorter incubation periods. Mice with intermediate incubation periods for vCJD prions had a mixture of the 2 strains. Both strains were serially transmitted in Tg1014 mice, which led to further reduction in incubation periods. Conversion of vCJD-like to sCJD-like strains was favored in Tg1014 mice more than in the Tg22372 line. The single amino acid difference therefore appears to offer selective pressure for propagation of the sCJD-like strain. Interpretation: These 2 Tg mouse lines provide relatively rapid models to study human prion diseases as well as the evolution of human prion strains. ANN NEUROL 2010;68:151,161 [source] Extensive astrocyte infection is prominent in human immunodeficiency virus,associated dementia,ANNALS OF NEUROLOGY, Issue 2 2009Melissa J. Churchill PhD Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction to detect HIV DNA in single astrocytes in vivo, we showed that astrocyte infection is extensive in subjects with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition, astrocyte infection frequency correlated with the severity of neuropathological changes and proximity to perivascular macrophages. Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis. Ann Neurol 2009;66:253,258 [source] | ||||||||||||||||||||||