High intrinsic oxidative stress may underlie selective vulnerability of the hippocampal CA1 region

Wang, Xinkun; Pal, Ranu; Chen, Xue-Wen; Limpeanchob, Nanteetip; Kumar, Keshava N.; Michaelis, Elias K.

doi:10.1016/j.molbrainres.2005.07.018

Cited by 101 publications

(87 citation statements)

References 50 publications

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“…Quantitative analysis of the cell count revealed significant reduction in neuronal number both in the hippocampal regions (CA1 and CA3) and the cerebellar cortex which support our previous findings (Mustapha et al, 2014; Azeez et al, 2016; Folarin et al, 2016). This result also shows more vulnerability of CA1 region to insults than CA3; this is because high intrinsic superoxide and endogenous ROS production occur in CA1 than CA3 region (Wilde et al, 1997; Wang et al, 2005). It is also reported that mitochondrial permeability transition pore of CA1 region is more sensitive to calcium homeostasis and this leads to active production of ROS (Mattiasson et al, 2003).…”

Section: Discussionmentioning

confidence: 77%

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

et al. 2017

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Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment. A total of 85 male BALB/c mice were used for the experiment and divided into three major groups of vanadium treated (intraperitoneally (i.p.) injected with 3 mg/kg body weight of sodium metavanadate and sacrificed every 3 months till 18 months); matched controls; and animals that were exposed to vanadium for 3 months and thereafter the metal was withdrawn. Brain tissues were obtained after animal sacrifice. Sagittal cut sections of paraffin embedded tissue (5 μm) were analyzed by the Laser ablation-inductively coupled plasma-mass spectrometry (LA–ICP–MS) to show the absorption and distribution of vanadium metal. Also, Haematoxylin and Eosin (H&E) staining of brain sections, and immunohistochemistry for Microglia (Iba-1), Astrocytes (GFAP), Neurons (Neu-N) and Neu-N + 4′,6-diamidine-2′-pheynylindole dihydrochloride (Dapi) Immunofluorescent labeling were observed for morphological and morphometric parameters. The LA–ICP–MS results showed progressive increase in vanadium uptake with time in different brain regions with prediction for regions like the olfactory bulb, brain stem and cerebellum. The withdrawal brains still show presence of vanadium metal in the brain slightly more than the controls. There were morphological alterations (of the layering profile, nuclear shrinkage) in the prefrontal cortex, cellular degeneration (loss of dendritic arborization) and cell death in the Hippocampal CA1 pyramidal cells and Purkinje cells of the cerebellum, including astrocytic and microglial activation in vanadium exposed brains which were all attenuated in the withdrawal group. With exposure into old age, the evident neuropathology was microgliosis, while progressive astrogliosis became more attenuated. We have shown that chronic administration of vanadium over a lifetime in mice resulted in metal accumulation which showed regional variabilities with time. The metal profile and pathological effects were not completely eliminated from the brain even after a long time withdrawal from vanadium metal.

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Section: Discussionmentioning

confidence: 77%

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

et al. 2017

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“…25 Acute ischemia leads to energy depletion because of a loss of oxygen and glucose with subsequent impaired generation of ATP, increased membrane permeability and the facilitated production of reactive oxygen species. 27 As a consequence of altered ATP supplies, changes in ion gradients lead to the accumulation of extracellular glutamate, and the resulting intracellular accumulation of Ca 2+ results in cytotoxicity. 28 Oxidative stress is the result of an imbalance between the generation of deleterious reactive oxygen and nitrogen species and the cell's compensatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Selective Neuronal Vulnerability of Human Hippocampal CA1 Neurons: Lesion Evolution, Temporal Course, and Pattern of Hippocampal Damage in Diffusion-Weighted MR Imaging

Bartsch

Döhring

Reuter

et al. 2015

J Cereb Blood Flow Metab

127

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The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n = 50), limbic encephalitis (n = 30), after status epilepticus (n = 17), and transient global amnesia (n = 53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.

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“…Moreover, the associations we found between mtDNA 8-oxo-dG and volumes of hippocampus and cerebellar gray matter are interesting in light of published work on the effect of oxidative stress on brain neurons. Hippocampal CA1 neurons are selectively vulnerable to oxidative stress (Wang et al, 2005; Wilde et al, 1997). Neurons in cerebellar gray matter (but not cerebral cortex) show a differential response to conditions involving oxidative stress: in particular, the cerebellar granule layer is sensitive to oxidative stress and can undergo extensive neuronal death (Wang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients

et al. 2016

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Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51 years; 81% with HIV RNA ≤50 copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3 T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets.

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High intrinsic oxidative stress may underlie selective vulnerability of the hippocampal CA1 region

Cited by 101 publications

References 50 publications

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

Selective Neuronal Vulnerability of Human Hippocampal CA1 Neurons: Lesion Evolution, Temporal Course, and Pattern of Hippocampal Damage in Diffusion-Weighted MR Imaging

Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients

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