Apolipoprotein D is Elevated in Oligodendrocytes in the Peri-Infarct Region after Experimental Stroke: Influence of Enriched Environment

Rickhag, Mattias; Deierborg, Tomas; Patel, Seema; Ruscher, Karsten; Wieloch, Tadeusz

doi:10.1038/sj.jcbfm.9600552

Cited by 49 publications

(44 citation statements)

References 40 publications

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“…81,82) Apo D is synthesized in oligodendrocytes and astrocytes of the CNS 83) and shows neurotrophic and synaptogenic effects in dorsal root ganglion neurons in vitro. 84) The levels of apo D are increased in the pre-frontal cortex of AD patients 85) and in brains of an animal model of Niemann-Pick type C disease, 86) without any change in the amount of apo E. The mRNA level and immunoreactivity of apo D is up-regulated in oligodendrocytes and astrocytes in the peri-infarct area of experimental stroke, 87,88) and the level of apo E is also increased in this area of animal stroke model. 89) The level of apo D in the brain of apo E knockout mice was increased 50-fold compared to that in wild type mice.…”

Section: Lipoproteins In the Cnsmentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFunctions of the central nervous system (CNS) are performed mainly by neurons and glia-primarily astrocytes, microglia and oligodendrocytes. It has been thought for a long time that glia only passively support neurons, but we now know that glia actively attend to assist in neuronal functions like synaptogenesis and neurotransmission. 1) Although it was believed that ca. 90% of the cells in the brain are glia and the rest of cells are neurons, Azevedo et al. recently reported that the numbers of neurons and non-neuronal cells (glia) are close to equal in human adult brain.2) Brain is the most cholesterol-rich organ in the body, and cholesterol metabolism in the CNS is tightly regulated between neurons and glia. [3][4][5][6][7] Imbalances in the metabolism of lipids, especially cholesterol, are closely linked to the development of several neurodegenerative disorders such as Alzheimer's disease, 8,9) Niemann-Pick type C disease 10) and Smith-Lemli Opitz syndrome. 11,12) In this review the regulation of lipid metabolism and the roles of glial lipoproteins in the CNS will be discussed. LIPID HOMEOSTASIS IN THE CNSThe system of lipid metabolism and transport in the CNS is different from that in peripheral tissues because the CNS is segregated from the peripheral circulation by the blood-brain barrier (BBB).13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS. Furthermore, in the plasma of subjects who had liver transplantation the genotype of apolipoprotein (apo) E was that of the donor, whereas the subjects retained the own apo E genotype in the cerebrospinal fluid (CSF).17) Moreover, lipoproteins in the CNS consist of only high density lipoprotein (HDL)-like particles in contrast to the circulation which contains very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL. It is known that the HDL-like particles in the CNS are secreted from glia (glial lipoproteins), mainly astrocytes and microglia, under normal conditions, [18][19][20] however lipoproteins can be secreted from neurons in vitro 21,22) and in vivo 23) under some specific conditions. Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The majority (70-80%) of cholesterol in the adult brain is in myelin formed by oligodendrocytes. 24)Thus, the activity of cholesterol synthesis in the CNS is the highest during the myelinogenesis. After myelination, cholesterol synthesis continues at very low level in the CNS, and occurs mainly in astrocytes. 5,13,24) Neurons do not efficiently synthesize cholesterol and rely on external source of cholesterol from astrocytes, 25) so that neurons take up cholesterol as lipoproteins via ...

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Section: Lipoproteins In the Cnsmentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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“…In shamoperated animals, equivalent brain regions were dissected, also designated as IC and PI (a schematic representation of IC and PI is included in the Results section). Whole cellular protein extractions from mice brains were performed as in Rickhag et al (2008). Interleukin-1b levels were determined by an electrochemiluminescence-coupled immunosorbent assay according to the manufacturer's instructions and using a SECTOR Imager 6,000 (Meso Scale Discovery, Gaithersburg, MD, USA).…”

Section: Interleukin-1b Immunosorbent Assaymentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Promotes Cell Death and Aggravates Neurologic Deficits after Experimental Stroke

Inácio

Ruscher

Leng

et al. 2010

J Cereb Blood Flow Metab

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Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif À/À mice does not affect interleukin-1b protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.

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“…12 Likewise, enriched housing initiated days after experimental stroke enhances long-term functional recovery, which occurs without decreasing infarct size. Here, the beneficial processes stimulate glia cells to encapsulate the infarct [13][14][15] or enhance neuronal plasticity. 16 Importantly, enriched housing has a profound effect on the inflammatory reponse after brain injury 14 and modulates cell genesis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Ruscher

Kuric

Liu

et al. 2013

J Cereb Blood Flow Metab

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After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3 þ ) and CD3 þ /CD4 þ T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.

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Apolipoprotein D is Elevated in Oligodendrocytes in the Peri-Infarct Region after Experimental Stroke: Influence of Enriched Environment

Cited by 49 publications

References 40 publications

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Macrophage Migration Inhibitory Factor Promotes Cell Death and Aggravates Neurologic Deficits after Experimental Stroke

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

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