nach oben

Erschienen in:

01.06.2012 | Original Paper

The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

verfasst von: Hilary A. Seifert, Christopher C. Leonardo, Aaron A. Hall, Derrick D. Rowe, Lisa A. Collier, Stanley A. Benkovic, Alison E. Willing, Keith R. Pennypacker

Erschienen in: Metabolic Brain Disease | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

Delayed neuronal death associated with stroke has been increasingly linked to the immune response to the injury. Splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective and significantly reduces neuroinflammation. The present study investigated whether splenic signaling occurs through interferon gamma (IFNγ). IFNγ was elevated early in spleens but later in the brains of rats following MCAO. Splenectomy decreased the amount of IFNγ in the infarct post-MCAO. Systemic administration of recombinant IFNγ abolished the protective effects of splenectomy with a concurrent increase in INFγ expression in the brain. These results suggest a role for spleen-derived IFNγ in stroke pathology.

Ajmo CT Jr, Vernon DO, Collier L, Pennypacker KR, Cuevas J (2006) Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats. Curr Neurovasc Res 3(2):89–98PubMedCrossRef

Ajmo CT Jr, Vernon DO, Collier L, Hall AA, Garbuzova-Davis S, Willing A, Pennypacker KR (2008) The spleen contributes to stroke-induced neurodegeneration. J Neurosci Res 86:2227–2234PubMedCrossRef

Bal-Price A, Brown GC (2001) Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci 21(17):6480–6491PubMed

Barres BA, Schmid R, Sendnter M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118(1):283–295PubMed

Becker KJ, Kindrick DL, Lester MP, Shea C, Ye ZC (2005) Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J Cereb Blood Flow Metab 25(12):1634–1644PubMedCrossRef

Becker KJ, Kalil AJ, Tanzi P, Zierath DK, Savos AV, Gee JM, Hadwin J, Carter KT, Shibata D, Cain KC (2011) Autoimmune Responses to the Brain After Stroke Are Associated With Worse Outcome. Stroke

Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-gamma. Annu Rev Immunol 15:749–795PubMedCrossRef

Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ (2001) Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 21(15):5528–5534PubMed

Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1362PubMedCrossRef

Duckworth EA, Butler TL, De Mesquita D, Collier SN, Collier L, Pennypacker KR (2005) Temporary focal ischemia in the mouse: technical aspects and patterns of Fluoro-Jade evident neurodegeneration. Brain Res 1042(1):29–36PubMedCrossRef

Gottschall PE, Yu X, Bing B (1995) Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture. J Neurosci Res 42(3):335–342PubMedCrossRef

Hall AA, Guyer AG, Leonardo CC, Ajmo CT Jr, Collier LA, Willing AE, Pennypacker KR (2009a) Human umbilical cord blood cells directly suppress ischemic oligodendrocyte cell death. J Neurosci Res 87(2):333–341PubMedCrossRef

Hall AA, Leonardo CC, Collier LA, Rowe DD, Willing AE, Pennypacker KR (2009b) Delayed treatments for stroke influence neuronal death in rat organotypic slice cultures subjected to oxygen glucose deprivation. Neuroscience 164(2):470–477PubMedCrossRef

Horiuchi M, Itoh A, Pleasure D, Itoh T (2006) MEK-ERK signaling is involved in interferon-gamma-induced death of oligodendroglial progenitor cells. J Biol Chem 281(29):20095–20106PubMedCrossRef

Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, Offner H (2007) T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab 27(11):1798–1805PubMedCrossRef

Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X (2007) Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery 141(1):32–40PubMedCrossRef

Lambertsen KL, Gregersen R, Meldgaard M, Clausen BH, Heibol EK, Ladeby R, Knudsen J, Frandsen A, Owens T, Finsen B (2004) A role for interferon-gamma in focal cerebral ischemia in mice. J Neuropathol Exp Neurol 63(9):942–955PubMed

Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, Hong NH, Kim JH, Ban JJ, Park HK, Kim SU, Park CG, Lee SK, Kim M, Roh JK (2008) Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain 131(Pt 3):616–629PubMedCrossRef

Leonardo CC, Hall AA, Collier LA, Ajmo CTJ, Willing AE, Pennypacker KR (2010) Human umbilical cord blood cell therapy blocks the morphological change and recruitment of CD-11b-expressing isolectin-binding proinflammatory cells after middle cerebral artery occlusion. J Neurosci Res 88(6):1213–1222PubMed

Li HL, Kostulas N, Huang YM, Xiao BG, van der Meide P, Kostulas V, Giedraitas V, Link H (2001) IL-17 and IFN-gamma mRNA expression is increased in the brain and systemically after permanent middle cerebral artery occlusion in the rat. J Neuroimmunol 116(1):5–14PubMedCrossRef

Li M, Li F, Luo C, Shan Y, Zhang L, Qian Z, Zhu G, Lin J, Feng H (2011) Immediate Splenectomy Decreases Mortality and Improves Cognitive Function of Rats After Severe Traumatic Brain Injury. J Trauma

Liesz A, Hagmann S, Zschoche C, Adamek J, Zhou W, Sun L, Hug A, Zorn M, Dalpke A, Nawroth P, Veltkamp R (2009a) The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation. Stroke 40(8):2849–2858PubMedCrossRef

Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, Giese T, Veltkamp R (2009b) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15(2):192–199PubMedCrossRef

Liesz A, Zhou W, Mracsko E, Karcher S, Bauer H, Schwarting S, Sun L, Bruder D, Stegemann S, Cerwenka A, Sommer C, Dalpke AH, Veltkamp R (2011) Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke. Brain 134(Pt 3):704–720PubMedCrossRef

Longa E, Weinstein P, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedCrossRef

Lucas SM, Rothwell NJ, Gibson RM (2006) The role of inflammation in CNS injury and disease. Br J Pharmacol 147(Suppl 1):S232–240PubMed

McCarthy KD, de Vellis J (1980) Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol 85(3):890–902PubMedCrossRef

Newcomb JD, Ajmo CT Jr, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2006) Timing of cord blood treatment after experimental stroke determines therapeutic efficacy. Cell Transplant 15(3):213–223PubMedCrossRef

Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD (2006) Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab 26(5):654–665PubMedCrossRef

Okuaki Y, Miyazaki H, Zeniya M, Ishikawa T, Ohkawa Y, Tsuno S, Sakaguchi M, Hara M, Takahashi H, Toda G (1996) Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat. Liver 16(3):188–194PubMed

Peterfalvi A, Molnar T, Banati M, Pusch G, Miko E, Bogar L, Pal J, Szereday L, Illes Z (2009) Impaired function of innate T lymphocytes and NK cells in the acute phase of ischemic stroke. Cerebrovasc Dis 28(5):490–498PubMedCrossRef

Ren X, Akiyoshi K, Vandenbark AA, Hurn PD, Offner H (2010) CD4 + FoxP3+ regulatory T-cells in cerebral ischemic stroke. Metab Brain Dis 26(1):87–90PubMedCrossRef

Rowe DD, Leonardo CC, Hall AA, Shahaduzzaman MD, Collier LA, Willing AE, Pennypacker KR (2010) Cord blood administration induces oligodendrocyte survival through alterations in gene expression. Brain Res 1366:172–188PubMedCrossRef

Savas MC, Ozguner M, Ozguner IF, Delibas N (2003) Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury. J Pediatr Surg 38(10):1465–1470PubMedCrossRef

Schmued LC, Albertson C, Slikker W Jr (1997) Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res 751(1):37–46PubMedCrossRef

Yang Z, Watanabe M, Nishiyama A (2005) Optimization of oligodendrocyte progenitor cell culture method for enhanced survival. J Neurosci Meth 149(1):50–56CrossRef

Yilmaz G, Arumugam TV, Stokes KY, Granger DN (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113(17):2105–2112PubMedCrossRef

Titel: The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling
verfasst von: Hilary A. Seifert
Christopher C. Leonardo
Aaron A. Hall
Derrick D. Rowe
Lisa A. Collier
Stanley A. Benkovic
Alison E. Willing
Keith R. Pennypacker
Publikationsdatum: 01.06.2012
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 2/2012
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-012-9283-0

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2012

Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury

A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy

Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats

Chronic cigarette smoke exposure enhances brain-derived neurotrophic factor expression in rats with traumatic brain injury

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram