|
| ||
|
|
||
Brain Pathology (brain + pathology)
Selected AbstractsBrain Pathology: Past, Present, and FutureBRAIN PATHOLOGY, Issue 2 2000Clayton A. Wiley No abstract is available for this article. [source] A role for the volume regulated anion channel in volume regulation in the murine CNS cell line, CADACTA PHYSIOLOGICA, Issue 2 2010V. L. Harvey Abstract Aim:, The role of the volume regulated anion channel (VRAC) in a model CNS neuronal cell line, CAD, was investigated. Methods:, Changes in cell volume following hypotonic challenges were measured using a video-imaging technique. The effect of the Cl, channel antagonists tamoxifen (10 ,m) and 4,4,-diisothiocyanatostilbene-2,2,-disulphonic acid (DIDS; 100 ,m) on regulatory volume decrease (RVD) were measured. The whole-cell voltage-clamp technique was used to characterize IClswell, the current underlying the VRAC. Results:, Using the video-imaging technique, CAD cells were found to swell and subsequently exhibit RVD when subjected to a sustained hypotonic challenge from 300 mOsmol kg,1 H2O to 210 mOsmol kg,1 H2O. In the presence of tamoxifen (10 ,m) or DIDS (100 ,m) RVD was abolished, suggesting a role for the VRAC. A hypotonic solution (230 mOsmol kg,1 H2O) evoked IClswell, an outwardly rectifying current displaying time-independent activation, which reversed upon return to isotonic conditions. The reversal potential (Erev) for IClswell was ,14.7 ± 1.4 mV, similar to the theoretical Erev for a selective Cl, conductance. IClswell was inhibited in the presence of DIDS (100 ,m) and tamoxifen (10 ,m), the DIDS inhibition being voltage dependent. Conclusions:, Osmotic swelling elicits an outwardly rectifying Cl, conductance in CAD cells. The IClswell observed in these cells is similar to that observed in other cells, and is likely to provide a pathway for the loss of Cl, which leads to water loss and RVD. As ischaemia, brain trauma, hypoxia and other brain pathologies can cause cell swelling, CAD cells represent a model cell line for the study of neuronal cell volume regulation. [source] Oncostatin M enhances the expression of prostaglandin E2 and cyclooxygenase-2 in astrocytes: Synergy with interleukin-1,, tumor necrosis factor-,, and bacterial lipopolysaccharideGLIA, Issue 4 2003Pavle Repovic Abstract Oncostatin M (OSM), a cytokine of the interleukin-6 family, is expressed in rheumatoid arthritis, multiple sclerosis, multiple myeloma, and other inflammatory and neoplastic conditions. Prostaglandin E2 (PGE2), an eicosanoid also associated with inflammation and cancer, has recently been shown to induce OSM expression. We report here that OSM in turn induces PGE2 production by astrocytes and astroglioma cells. More importantly, in combination with the inflammatory mediators IL-1,, tumor necrosis factor-,, and lipopolysaccharide, OSM exhibits a striking synergy, resulting in up to 50-fold higher PGE2 production by astrocytes, astroglioma, and neuroblastoma cell lines. Enhanced PGE2 production by OSM and IL-1, treatment is explained by their effect on cyclooxygenase-2 (COX-2), an enzyme that catalyzes the committed step in PGE2 synthesis. Of the enzymes involved in PGE2 biosynthesis, only COX-2 mRNA and protein levels are synergistically amplified by OSM and IL-1,. Nuclear run-on assays demonstrate that OSM and IL-1, synergistically upregulate transcription of the COX-2 gene, and the mRNA stability assay indicates that COX-2 mRNA is posttranscriptionally stabilized by OSM and IL-1,. To effect synergy on the PGE2 level, OSM signals in part through its gp130/OSMR, receptor, since neutralizing antibodies against gp130 and OSMR,, but not LIFR,, decrease PGE2 production in response to OSM plus IL-1,. SB202190 and U0126, inhibitors of p38 MAPK and ERK1/2 activation, respectively, inhibit IL-1, and OSM upregulation of COX-2 and PGE2, indicating that these MAPK cascades are utilized by both stimuli. This mechanism of PGE2 amplification may be active in brain pathologies where both OSM and IL-1, are present, such as glioblastomas and multiple sclerosis. GLIA 42:433,446, 2003. © 2003 Wiley-Liss, Inc. [source] Ca2+ -induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex IJOURNAL OF NEUROCHEMISTRY, Issue 3 2005Tatyana V. Votyakova Abstract Mitochondrial complex I dysfunction has been implicated in a number of brain pathologies, putatively owing to an increased rate of reactive oxygen species (ROS) release. However, the mechanisms regulating the ROS burden are poorly understood. In this study we investigated the effect of Ca2+ loads on ROS release from rat brain mitochondria with complex I partially inhibited by rotenone. The addition of 20 nm rotenone to brain mitochondria increased ROS release. Ca2+ (100 µm) alone had no effect on ROS release, but greatly potentiated the effects of rotenone. The effect of Ca2+ was decreased by ruthenium red. Ca2+ -challenged mitochondria lose about 88% of their glutathione and 46% of their cytochrome c under these conditions, although this depends only on Ca2+ loading and not complex I inhibition. ADP in combination with oligomycin decreased the loss of glutathione and cytochrome c and free radical generation. Cyclosporin A alone was ineffective in preventing these effects, but augmented the protection provided by ADP and oligomycin. Non-specific permeabilization of mitochondria with alamethicin also increased the ROS signal, but only when combined with partial inhibition of complex I. These results demonstrate that Ca2+ can greatly increase ROS release by brain mitochondria when complex I is impaired. [source] Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibitionJOURNAL OF PINEAL RESEARCH, Issue 2 2003Seung-Yun Chung Abstract:,The antioxidant and anti-inflammatory effects of melatonin on kainic acid (KA)-induced neurodegeneration in the hippocampus were evaluated in vivo. It has been suggested that the pineal secretory product, melatonin, protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors, and from oxidative stress-induced DNA damage and apoptosis. In this study, we injected 10 mg/kg kainate intraperitoneally (i.p.) into adult male Sprague-Dawley rats. This results in selective neuronal degeneration accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of melatonin in preventing KA-induced neurodegeneration, oxidative stress and neuroinflammation in the hippocampus. Melatonin (2.5 mg/kg, i.p.) was given 20 min before, immediately after, and 1 and 2 hr after KA administration. Rats were killed 72 hr later and their hippocampi were examined for evidence of DNA damage (in situ dUTP end-labeling, i.e. TUNEL staining), cell viability (hematoxylin and eosin staining), and microglial (isolectin-B4 histochemistry) and astroglial responses (glial fibrillary acidic protein immunohistochemistry), as well as lipid peroxidation (4-hydroxynonenal immunohistochemistry). A cumulative dose of 10 mg/kg melatonin attenuates KA-induced neuronal death, lipid peroxidation, and microglial activation, and reduces the number of DNA breaks. A possible mechanism for melatonin-mediated neuroprotection involves its antioxidant and anti-inflammatory actions. The present data suggest that melatonin is potentially useful in the treatment of acute brain pathologies associated with oxidative stress-induced neuronal damage such as epilepsy, stroke, and traumatic brain injury. [source] Pulsed Z-spectroscopic imaging of cross-relaxation parameters in tissues for human MRI: Theory and clinical applicationsMAGNETIC RESONANCE IN MEDICINE, Issue 5 2002Vasily L. Yarnykh Abstract A new method of pulsed Z-spectroscopic imaging is proposed for in vivo visualization and quantification of the parameters describing cross-relaxation between protons with liquid-like and solid-like relaxation properties in tissues. The method is based on analysis of the magnetization transfer (MT) effect as a function of the offset frequency and amplitude of a pulsed off- resonance saturation incorporated in a spoiled gradient-echo MRI pulse sequence. The theoretical concept of the method relies on an approximated analytical model of pulsed MT that provides a simple three-parameter equation for a pulsed steady-state Z-spectrum taken far from resonance. Using this model, the parametric images of cross-relaxation rate constant, content, and T2 of the semisolid proton fraction can be reconstructed from a series of MT-weighted images and a coregistered T1 map. The method was implemented on a 0.5 T clinical MRI scanner, and it provided high-quality 3D parametric maps within an acceptable scanning time. The estimates of cross-relaxation parameters in brain tissues were shown to be quantitatively consistent with the literature data. Clinical examples of the parametric images of human brain pathologies (multiple sclerosis and glioma) demonstrated high tissue contrast and clear visualization of the lesions. Magn Reson Med 47:929,939, 2002. © 2002 Wiley-Liss, Inc. [source] RIC-3 and nicotinic acetylcholine receptors: Biogenesis, properties, and diversityBIOTECHNOLOGY JOURNAL, Issue 12 2008Millet Treinin Dr.Article first published online: 27 OCT 200 Abstract Nicotinic acetylcholine receptors (nAChRs) belong to a diverse and widely expressed family of ion channels. These receptors are pentamers assembled from multiple combinations of subunits, with different subunit compositions producing receptors having different properties and functions. The diverse functions of nAChRs include an essential role in excitation of skeletal muscles and many modulatory roles throughout the central nervous system. Nicotinic receptors are also implicated in a number of brain pathologies such as epilepsy, schizophrenia, and Alzheimer's disease. Thus, it is important to understand the cellular mechanisms controlling both the numbers and the properties of surface expressed nAChRs. Genetic analysis in Caenorhabditis elegans identified a number of proteins specifically needed for biogenesis of nAChRs. Among these proteins is RIC-3, a member of a family of proteins having conserved structure and function. RIC-3 influences both surface expression and properties of nAChRs and its effects are subtype specific. Here we suggest that receptor-specific chaperones such as RIC-3 may play important roles in controlling receptor diversity by selectively regulating surface expression of nAChRs having specific subunit compositions. [source] Severe brain pathology: Underdiagnosed in psychiatric patients?ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2005Lars Vedel Kessing No abstract is available for this article. [source] Status Epilepticus,Induced Neuronal Loss in Humans Without Systemic Complications or EpilepsyEPILEPSIA, Issue 8 2000Denson G. Fujikawa Summary: Purpose: To determine the regional distribution of neuronal damage caused strictly by status epilepticus (SE) without systemic complications, underlying brain pathology, or a history of preexisting epilepsy. Methods: The medical records and electroencephalograms (EEGs) of three deceased patients who developed SE in the hospital were reviewed. Their brains were formalin-fixed, and 17 brain regions were selected, embedded in paraffin, and sectioned. Alternate sections were stained with either hematoxylin and eosin and cresyl violet to determine the extent of neuronal loss and gliosis or glial fibrillary astrocytic protein to confirm the extent of astrocytic proliferation. Results: The three patients died 11 to 27 days after the onset of focal motor SE; none had hypotension, hypoxemia, hypoglycemia, or significant hyperthermia. Two patients had no prior seizures and no underlying brain pathology. The third patient, who had leptomeningeal carcinomatosis, had one seizure 2 months before the onset of SE. The duration of SE was 8.8 hours to 3 days. EEGs showed unilateral temporal lobe sharp-wave discharges in one patient and independent temporal lobe sharp-wave discharges bilaterally in the other two patients. In addition to widespread neuronal loss and reactive gliosis in the hippocampus, amygdala, dorsomedial thalamic nucleus, and Purkinje cell layer of the cerebellum, we report for the first time periamygdaloid (piriform) and entorhinal cortical damage occurring acutely after SE in humans. Conclusions: In the absence of systemic complications or preexisting epilepsy, SE produces neuronal loss in a distribution similar to that from domoic acid-induced SE in humans and from kainic acid- and pilocarpine-induced SE in rats. [source] Isolated sulfite oxidase deficiency: mutation analysis and DNA-based prenatal diagnosisPRENATAL DIAGNOSIS, Issue 5 2002J. L. Johnson Abstract Isolated sulfite oxidase deficiency is an autosomal recessive, neurological disorder resulting from a defect in SUOX, the gene encoding the enzyme that catalyzes the terminal reaction in the sulfur amino acid degradation pathway. In its classical, severe form, sulfite oxidase deficiency leads to intractable seizures, severe and progressive brain pathology and death at an early age. We report here on clinical features and mutational analysis of the genetic defect in a newborn with sulfite oxidase deficiency. Cultured fibroblasts from this patient exhibited no detectable sulfite oxidase activity, and a unique four base pair deletion was present in the cDNA isolated from the same source. Identification of the same genetic defect in a heterozygous state in each of the parents and the monitoring of subsequent pregnancies in this family by DNA-based prenatal diagnosis are also described. The deletion mutation was identified in a homozygous state in uncultured chorionic villus tissue from the second pregnancy that was subsequently terminated. In the third pregnancy, the presence of sulfite oxidase activity and identification of the mutation in a heterozygous state suggested that the fetus was not affected. This pregnancy resulted in the birth of a normal child. Copyright © 2002 John Wiley & Sons, Ltd. [source] Adult neural stem cells and their role in brain pathology,THE JOURNAL OF PATHOLOGY, Issue 2 2009G Yadirgi Abstract Stem cells are multipotent cells that can give rise to a differentiated progeny as well as self-renew. The balanced coordination of these two stem cell fates is essential for embryonic development and tissue homeostasis in the adult. Perturbed stem cell function contributes significantly to a variety of pathological conditions, eg impaired self-renewal capacity due to cellular senescence contributes to ageing, and degenerative diseases or impaired stem cell differentiation by oncogenic mutations contribute to cancer formation. This review focuses on the molecular mechanisms involved in regulating the normal function of neural stem cells in the adult mammalian brain and on the involvement of these cells in brain pathology. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of aging cohortANNALS OF NEUROLOGY, Issue 2 2010Hillary Dolan MA Objective Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts. Methods We examined the relationship between systemic atherosclerosis, Alzheimer type pathology, and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging, a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies. Results Using a quantitative analysis of atherosclerosis in the aorta, heart, and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible. Interpretation Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer pathology and stroke through which vascular changes may influence dementia risk. [source] First appraisal of brain pathology owing to A30P mutant alpha-synucleinANNALS OF NEUROLOGY, Issue 5 2010Kay Seidel PhD Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha-synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha-synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha-synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha-synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684,689 [source] Olfactory epithelium amyloid-, and paired helical filament-tau pathology in Alzheimer diseaseANNALS OF NEUROLOGY, Issue 4 2010Steven E. Arnold MD Objective Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, ,-synuclein, and amyloid-, lesions occur early and severely in cerebral regions of the olfactory system, and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, and disease specificity, and the relationships of OE pathology to brain pathology have not been established. Methods We investigated the pathological expression of amyloid-,, PHFtau, ,-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. Results Amyloid-, was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. ,-Synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-, and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical A, and PHFtau lesion ratings in the brain. Interpretation These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-, and PHFtau measurement in OE as a biomarker for AD. ANN NEUROL 2010;67:462,469 [source] Amelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptideARTHRITIS & RHEUMATISM, Issue 12 2009Smadar Lapter Objective Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE-associated CNS pathology in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity-determining region), on these manifestations. Methods Histopathologic analyses of brains from lupus-prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed. The messenger RNA expression of SLE-associated cytokines and apoptosis-related molecules from the hippocampi was determined. Anxiety-like behavior was assessed by open-field tests and dark/light transfer tests, and memory deficit was assessed using a novel object recognition test. Results Infiltration was evident in the hippocampi of the lupus-afflicted mice, and the presence of CD3+ T cells as well as IgG and complement C3 complex deposition was observed. Furthermore, elevated levels of gliosis and loss of neuronal nuclei immunoreactivity were also observed in the hippocampi of the mice with lupus. Treatment with hCDR1 ameliorated the histopathologic changes. Treatment with hCDR1 down-regulated the high expression of interleukin-1, (IL-1,), IL-6, IL-10, interferon-,, transforming growth factor ,, and the proapoptotic molecule caspase 8 in the hippocampi of the mice with lupus, and up-regulated expression of the antiapoptotic bcl -xL gene. Diseased mice exhibited increased anxiety-like behavior and memory deficit. Treatment with hCDR1 improved these parameters, as assessed by behavior tests. Conclusion Treatment with hCDR1 ameliorated CNS pathology and improved the tested cognitive and mood-related behavior of the mice with lupus. Thus, hCDR1 is a novel candidate for the treatment of CNS lupus. [source] Pre-clinical Dementia: Does it Exist?AUSTRALASIAN JOURNAL ON AGEING, Issue 1 2001Louise M. Waite Identification of syndromes that will progress to dementia carries immense importance for the management of these diseases when therapies are available and for future research into effective early prevention. Evidence supporting the presence of a preclinical phase for dementia has arisen from a range of different areas. Clinical and epidemiological studies have identified both cognitive and neurological abnormalities which predict the future development of dementia. Similarly, various neuroimaging techniques have identified abnormalities in asymptomatic subjects with significant risk for developing Alzheimer's disease and subjects who show mild cognitive deficits. Neuropathological series are hampered by non-representative study populations and poor antemortem data but in studies where informants have been utilised to provide details of subjects' antemortem cognitive function, evidence indicates that the presence of brain pathology is associated with cognitive deficits. This paper reviews the current literature exploring the presence of a pre-clinical phase for dementia, identifies the weaknesses in this research and provides suggestions for future research. [source] Cognitive outcome at 2 years of age in Finnish infants with very low birth weight born between 2001 and 2006ACTA PAEDIATRICA, Issue 3 2010P Munck Abstract Aim:, To study cognitive outcome of premature, very low birth weight (VLBW) infants in relation to parental education and neonatal data. Methods:, A regional cohort of 182 VLBW infants born between 2001 and 2006 was followed up. Brain ultrasounds (US) were examined serially until term age and brain magnetic resonance imaging at term age. Neurological status was examined systematically. Cognitive development was assessed using the Mental Developmental Index (MDI) of Bayley Scales at 2 years of corrected age. A total of 192 healthy full-term (FT) controls were assessed with the MDI at 2 years of age. Results:, The mean MDI in VLBW infants was 101.7 (SD 15.4), which was lower compared with FT controls (109.8, SD 11.7, p < 0.001). In regression analysis of the demographic and medical data of VLBW infants, postnatal corticosteroids (p = 0.04), intestinal perforation (p = 0.03) and major brain pathology (p = 0.02) were negatively associated with the MDI. In VLBW infants, the prevalence of neurodevelopmental impairment was 9.9% (3.3% MDI below 70, 7.1% cerebral palsy, 2.2% hearing aid, no blind infants). Conclusion:, Cognitive development of VLBW infants seemed to have improved in comparison with earlier publications, but it differed from the FT controls. Neonatal factors affected cognitive development. Therefore, updated regional follow-up data are important for clinicians. [source] | |||||||||||||||||||||||||