Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia.

Abstract:

:Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eIF2alpha (S51D) mimicking phosphorylated eIF2alpha induces apoptosis, and expression of non-phosphorylatable eIF2alpha (S51A) blocks induction of apoptosis. An early event in initiating apoptosis is the release of cytochrome c from mitochondria, and cytochrome c release corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. At present the signaling pathways leading to this are not well defined. We hypothesized that persistent eIF2alpha(P) reflects injury mechanisms that are causally upstream of release of cytochrome c and induction of apoptosis. At 4 h of reperfusion following 10-min cardiac arrest, vulnerable neurons in the striatum, hippocampal hilus and CA1 showed colocalized intense immunostaining for both persistent eIF2alpha(P) and cytoplasmic cytochrome c, while resistant neurons in the dentate gyrus and elsewhere did not immunostain for either. A lower intensity of persistent eIF2alpha(P) immunostaining was present in cortical layer V pyramidal neurons without cytoplasmic cytochrome c, possibly reflecting the lesser vulnerability of this area to ischemia. We did not observe cytoplasmic cytochrome c in any neurons that did not also display persistent eIF2alpha(P) immunostaining. Because phosphorylation of eIF2alpha during early brain reperfusion is carried out by PERK, these findings suggest that there is prolonged activation of the unfolded protein response in the reperfused brain.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Page AB,Owen CR,Kumar R,Miller JM,Rafols JA,White BC,DeGracia DJ,Krause GS

doi

10.1007/s00401-003-0693-2

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

8-16

issue

1

eissn

0001-6322

issn

1432-0533

journal_volume

106

pub_type

杂志文章
  • Alzheimer paired helical filaments: identification of polypeptides with monoclonal antibodies.

    abstract::Paired helical filaments (PHF) were isolated from autopsied brain of cases of Alzheimer dementia, and their polypeptides were identified with monoclonal antibodies to PHF by Western blots. The PHF polypeptide profile consisted of several bands with a size difference of less than 5 kilodalton (kDa) between adjacent ban...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00690830

    authors: Grundke-Iqbal I,Wang GP,Iqbal K,Tung YC,Wisniewski HM

    更新日期:1985-01-01 00:00:00

  • Distribution patterns of tau pathology in progressive supranuclear palsy.

    abstract::Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PS...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-020-02158-2

    authors: Kovacs GG,Lukic MJ,Irwin DJ,Arzberger T,Respondek G,Lee EB,Coughlin D,Giese A,Grossman M,Kurz C,McMillan CT,Gelpi E,Compta Y,van Swieten JC,Laat LD,Troakes C,Al-Sarraj S,Robinson JL,Roeber S,Xie SX,Lee VM,Trojan

    更新日期:2020-08-01 00:00:00

  • Distinct conformers of transmissible misfolded SOD1 distinguish human SOD1-FALS from other forms of familial and sporadic ALS.

    abstract::Evidence of misfolded wild-type superoxide dismutase 1 (SOD1) has been detected in spinal cords of sporadic ALS (sALS) patients, suggesting an etiological relationship to SOD1-associated familial ALS (fALS). Given that there are currently a number of promising therapies under development that target SOD1, it is of cri...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-016-1623-4

    authors: Ayers JI,Diamond J,Sari A,Fromholt S,Galaleldeen A,Ostrow LW,Glass JD,Hart PJ,Borchelt DR

    更新日期:2016-12-01 00:00:00

  • Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo.

    abstract::Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of inflammation. While COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Although COX-1 expression is observed in normal tissue, enhanced COX-2 expression has been attributed a key...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010051075

    authors: Deininger MH,Weller M,Streffer J,Mittelbronn M,Meyermann R

    更新日期:1999-09-01 00:00:00

  • Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices.

    abstract::Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which id...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00308919

    authors: Maier H,Morimura T,Ofner D,Hallbrucker C,Kitz K,Budka H

    更新日期:1990-01-01 00:00:00

  • Correlation of morphologic brain lesions with physiologic alterations and blood-brain barrier impairment in 3-nitropropionic acid toxicity in rats.

    abstract::3-Nitropropionic acid (NPA), a toxin which irreversibly inhibits the Krebs cycle enzyme succinate dehydrogenase, causes severe neurologic disease and a specific pattern of morphologic brain damage when given subcutaneously to rats. To determine whether hypotension or hypoxemia were necessary for development of morphol...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00688340

    authors: Hamilton BF,Gould DH

    更新日期:1987-01-01 00:00:00

  • Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG).

    abstract::X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located on Xp22.13. Arx-null mice show loss of tangential migration of GABAergic interneurons, presumably being related to caudal ganglionic eminence tangential migration. In the ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-008-0382-2

    authors: Okazaki S,Ohsawa M,Kuki I,Kawawaki H,Koriyama T,Ri S,Ichiba H,Hai E,Inoue T,Nakamura H,Goto Y,Tomiwa K,Yamano T,Kitamura K,Itoh M

    更新日期:2008-10-01 00:00:00

  • Axonal inclusions in spinocerebellar ataxia type 3.

    abstract::Protein aggregation is a major pathological hallmark of many neurodegenerative disorders including polyglutamine diseases. Aggregation of the mutated form of the disease protein ataxin-3 into neuronal nuclear inclusions is well described in the polyglutamine disorder spinocerebellar ataxia type 3 (SCA3 or Machado-Jose...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-010-0717-7

    authors: Seidel K,den Dunnen WF,Schultz C,Paulson H,Frank S,de Vos RA,Brunt ER,Deller T,Kampinga HH,Rüb U

    更新日期:2010-10-01 00:00:00

  • Intermitochondrial septate structures in dystrophic axons.

    abstract::Intermitochondrial septate structures were found in the dystrophic axons of two cases of infantile neuroaxonal dystrophy. Septate structures were previously seen in some tumors (glioblastomas and Schwannomas) and several organs of vertebrates and invertebrates, but never in human central nervous system (CNS). The stru...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00688007

    authors: Ramos PL,Wisniewski K,Jervis GA,Wisniewski HM

    更新日期:1980-01-01 00:00:00

  • Papillary neuroepithelial tumor of the pineal region. A case report.

    abstract::We present here an unusual case of papillary neuroepithelial tumor of the pineal region. The patient was a 29-year-old female who presented with headaches. A computed tomography scan revealed a tumorous lesion at the pineal region and hydrocephalus. The resected tumor was composed of columnar and cuboidal cells showin...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-004-0898-z

    authors: Shibahara J,Todo T,Morita A,Mori H,Aoki S,Fukayama M

    更新日期:2004-10-01 00:00:00

  • Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration.

    abstract::This report presents the largest series of consecutive, neuropathologically confirmed cases of frontotemporal degeneration (FTD). Prior studies have found dementia lacking distinctive histology (DLDH) to be the most common pathology underlying the clinical diagnosis of FTD. In this series of 76 cases, 29 (38%) were fo...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-004-0900-9

    authors: Lipton AM,White CL 3rd,Bigio EH

    更新日期:2004-11-01 00:00:00

  • Expression of the cytokine leukemia inhibitory factor and pro-apoptotic insulin-like growth factor binding protein-3 in Alzheimer's disease.

    abstract::Amyloid-beta (Abeta) deposition in cerebral blood vessel walls is one of the key features of Alzheimer's disease (AD). Abeta(1-40) carrying the "Dutch" mutation (DAbeta(1-40)) induces rapid degeneration of cultured human brain pericytes (HBP). To study the mechanisms of this Abeta-induced toxicity, a comparative cDNA ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-002-0585-x

    authors: Rensink AA,Gellekink H,Otte-Höller I,ten Donkelaar HJ,de Waal RM,Verbeek MM,Kremer B

    更新日期:2002-11-01 00:00:00

  • Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation.

    abstract::Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explor...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-015-1411-6

    authors: Matosin N,Fernandez-Enright F,Fung SJ,Lum JS,Engel M,Andrews JL,Huang XF,Weickert CS,Newell KA

    更新日期:2015-07-01 00:00:00

  • Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical course, neuropathology and brain lipid composition in this Gaucher disease variant.

    abstract::Glucosylceramide lipidosis results from a defective lysosomal degradation of this glycolipid. Lipid degradation is controlled by two components, the enzyme beta-glucocerebrosidase and a sphingolipid activator protein. While most Gaucher cases are due to mutations within the gene that codes for the lysosomal enzyme, on...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050960

    authors: Pàmpols T,Pineda M,Girós ML,Ferrer I,Cusi V,Chabás A,Sanmarti FX,Vanier MT,Christomanou H

    更新日期:1999-01-01 00:00:00

  • Transient axonal injury in the absence of demyelination: a correlate of clinical disease in acute experimental autoimmune encephalomyelitis.

    abstract::Axonal degeneration contributes to the transient and permanent neurological deficits seen in multiple sclerosis, an inflammatory disease of the central nervous system. To study the immunological mechanisms causing axonal degeneration, we induced experimental autoimmune encephalomyelitis (EAE) in wildtype Lewis rats an...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-006-0047-y

    authors: Aboul-Enein F,Weiser P,Höftberger R,Lassmann H,Bradl M

    更新日期:2006-06-01 00:00:00

  • In vivo diagnosis of Kufs' disease by extracerebral biopsies.

    abstract::In almost all of the earlier reported cases of Kufs' disease, the adult form of ceroid lipofuscinosis, the diagnosis was ascertained by cerebral tissue examination, while peripheral biopsy examination revealed an apparent poor diffusion of specific lipofuscinic deposits, the finger print profiles (FPs). We report the ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050866

    authors: Gelot A,Maurage CA,Rodriguez D,Perrier-Pallisson D,Larmande P,Ruchoux MM

    更新日期:1998-07-01 00:00:00

  • GM1-gangliosidosis in a cross-bred dog confirmed by detection of GM1-ganglioside using electrospray ionisation-tandem mass spectrometry.

    abstract::The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010000187

    authors: Whitfield P,Johnson AW,Dunn KA,Delauche AJ,Winchester BG,Franklin RJ

    更新日期:2000-10-01 00:00:00

  • Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma.

    abstract::Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-011-0802-6

    authors: Schindler G,Capper D,Meyer J,Janzarik W,Omran H,Herold-Mende C,Schmieder K,Wesseling P,Mawrin C,Hasselblatt M,Louis DN,Korshunov A,Pfister S,Hartmann C,Paulus W,Reifenberger G,von Deimling A

    更新日期:2011-03-01 00:00:00

  • Vascular changes in acute Wernicke's encephalopathy.

    abstract::The nature and distribution of vascular changes in acute Wernicke's encephalopathy (WE) were analyzed in three autopsy cases. Lesions of the lateral vestibular nucleus of the medulla oblongata (three cases) and lateral ventricular wall (one case) were examined by reconstruction of 200 serial sections, and the capillar...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00307646

    authors: Okeda R,Taki K,Ikari R,Funata N

    更新日期:1995-01-01 00:00:00

  • Inflammatory myopathy with abundant macrophages and dermatomyositis: two stages of one disorder or two distinct entities?

    abstract::Inflammatory myopathy with abundant macrophages (IMAM) and dermatomyositis (DM) are considered to represent related disorders, since they share inflammatory infiltrates and skin alterations. In order to get more insight into these disorders, we addressed the cellular composition of the inflammatory infiltrates in musc...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-009-0570-8

    authors: Brunn A,Hans VJ,Vogelgesang S,Deckert M

    更新日期:2009-12-01 00:00:00

  • Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation.

    abstract::Cryostat sections of 12 gliomas and of 3 peritumoral brain tissue samples were investigated for mononuclear cell infiltration by immunohistochemistry, concentrating on cells expressing monocyte/macrophage markers. Only low numbers of T cells were detected in the tumors, whereas in average 20%-30% of all cells present ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00294647

    authors: Morimura T,Neuchrist C,Kitz K,Budka H,Scheiner O,Kraft D,Lassmann H

    更新日期:1990-01-01 00:00:00

  • Neuronal accumulation of silver in brains of progeny from argyric rats.

    abstract::Using a photochemical method silver was demonstrated in the brains of 1-, 14-, and 45-day-old rats which had been exposed to silver on gestational days 18 and 19. In the brain tissue of new-born rats, silver was found in the lysosomes of neurons and astroglia. Minor changes in the anatomic distribution of silver were ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00691995

    authors: Rungby J,Danscher G

    更新日期:1983-01-01 00:00:00

  • Pituitary growth hormone cell adenoma with cytoplasmic tubular aggregates in the capillary endothelium.

    abstract::Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00684545

    authors: Kovacs K,Horvath E,Pritzker KP,Schwartz ML

    更新日期:1977-01-31 00:00:00

  • Changes in the cytoskeletal proteins, sarcoplasmic reticulum, and capillaries in acute relaxant-steroid myopathy (ARSM) in contrast to the corticosteroid myopathy.

    abstract::Since we reported a case of acute relaxant-steroid myopathy (ARSM) in 1994, we continued histological studies and compared the findings with those in a case of corticosteroid myopathy (CM). It was revealed that (1) dystrophin, spectrin, beta dystroglycan, and sarcoglycans on the cell surface were decreased, (2) regula...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010051022

    authors: Matsubara S,Kitaguchi T,Isozaki E,Miyamoto K,Hirai S

    更新日期:1999-05-01 00:00:00

  • Neuropathology of mice with targeted disruption of Hexa gene, a model of Tay-Sachs disease.

    abstract::A murine model of Tay-Sachs disease, the prototype of the GM2 gangliosidoses, was produced through the targeted disruption of the Hexa gene encoding the subunit of alpha-hexosaminidase A. The mice were completely devoid of beta-hexosaminidase A activity and accumulated GM2 ganglioside in the CNS in an age-dependent ma...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00309622

    authors: Taniike M,Yamanaka S,Proia RL,Langaman C,Bone-Turrentine T,Suzuki K

    更新日期:1995-01-01 00:00:00

  • Creutzfeldt-Jakob disease in a patient with an R208H mutation of the prion protein gene (PRNP) and a 17-kDa prion protein fragment.

    abstract::A case of Creutzfeldt-Jakob disease (CJD) with a rare mutation of the prion protein (PrP) gene (PRNP) at codon 208 (R208H) is described. By comparison with two preceding reports, the case described here displayed two distinct biochemical and neuropathological features. Western blot analysis of brain homogenates showed...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-004-0978-0

    authors: Roeber S,Krebs B,Neumann M,Windl O,Zerr I,Grasbon-Frodl EM,Kretzschmar HA

    更新日期:2005-04-01 00:00:00

  • [The effect of piromen on the flial-mesenchymal scar in the cortex of hamsters].

    abstract::In the present work the effect of Piromen is studied on the formation of the glial-mesenchymal scar in the experimentally injuried cortex of hamsters. The uniform effect of the bacterial polysaccharide is suggested in a strong and lasting stimulation of proliferating reactive cells in the traumatic area. The excessive...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00684561

    authors: von Cramon D

    更新日期:1975-01-01 00:00:00

  • The neuropathology of cerebrotendinous xanthomatosis revisited: a case report and review of the literature.

    abstract::Cerebrotendinous xanthomatosis (CTX), a rare autosomal-recessive lipid storage disease, has been well characterized clinically and biochemically, and recently also from the molecular biological aspect. However, only a very few publications deal with its neuropathology, and views on its pathogenesis vary. Based on a re...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00294324

    authors: Soffer D,Benharroch D,Berginer V

    更新日期:1995-01-01 00:00:00

  • Fine structure of intercellular junctions and blood vessels in medulloblastomas.

    abstract::Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endoth...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00685966

    authors: Hassoun J,Hirano A,Zimmerman HM

    更新日期:1975-10-27 00:00:00

  • Ultrastructure of pineal parenchymal neoplasms.

    abstract::The fine structures of two pineal parenchymal neoplasms has been described. The tumors contained a predominance of small, poorly differentiated cells with prominent nuclei and scanty cytoplasm. These cells were similar to those found in medulloblastomas, primitive cerebral neuroectodermal tumors, and fetal cerebellum ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00699239

    authors: Markesbery WR,Haugh RM,Young AB

    更新日期:1981-01-01 00:00:00