A novel mechanism of FK506-mediated neuroprotection: downregulation of cytokine expression in glial cells

Glia
Malgorzata Zawadzka, Bozena Kaminska

Abstract

Immunosuppressant FK506 is neuroprotective in experimental models of cerebral ischemia, but the molecular mechanisms underlying this neuroprotection remain unknown. We have demonstrated that FK506 inhibits the signaling pathways that regulate hypertrophic/proliferative responses in cultured astrocytes. Ischemia/reperfusion injury is associated with the proliferation and hypertrophy of astrocytes and with inflammatory responses. In the present work, we sought to determine whether FK506 neuroprotection after middle cerebral artery occlusion (MCAo) in rat is mediated via suppression of glia activation and changes in cytokine expression. Neurological deficits, infarct size, and astrocyte/microglial response were quantified in rats subjected to 90 min of MCAo. Changes in the mRNA expression of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in ipsilateral and contralateral cortices were determined by reverse transcription-polymerase chain reaction (RT-PCR). FK506 administered at 1 mg/kg, 60 min after MCAo, produced a significant improvement in neurological function and reduction of infarct volume. In FK506-treated rats, a significant reduction of IL-1beta, IL-6, and TNF-alpha expression was observed 1...Continue Reading

References

Mar 1, 1990·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R A SwansonF R Sharp
Jan 1, 1989·Stroke; a Journal of Cerebral Circulation·E Z LongaR Cummins
May 1, 1986·Stroke; a Journal of Cerebral Circulation·J B BedersonH Bartkowski
Aug 1, 1995·Neuropathology and Applied Neurobiology·J GehrmannG W Kreutzberg
Jan 1, 1995·Nature Medicine·S H Snyder, D M Sabatini
Jan 1, 1993·Stroke; a Journal of Cerebral Circulation·T N LinC Y Hsu
Apr 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·K TanakaT Dembo
May 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H UnoM Sugita
Feb 20, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·G P SchielkeA L Betz
May 30, 1998·Journal of Neuroscience Methods·T SaitoT Nemoto
Oct 7, 1998·Progress in Neurobiology·G StollM Schroeter
Dec 1, 1998·The Journal of Physiology·N J Rothwell
May 6, 1999·Cellular and Molecular Life Sciences : CMLS·S F Göthel, M A Marahiel
May 26, 1999·Progress in Neurobiology·G Stoll, S Jander
Aug 11, 1999·Trends in Neurosciences·U DirnaglM A Moskowitz
Feb 11, 2000·Brain Pathology·H Kato, W Walz
Aug 10, 2000·Trends in Cell Biology·S Desagher, J C Martinou
Aug 8, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·J S BeechD K Menon
Jan 5, 2002·Journal of Biochemistry·Futoshi ShibasakiHiroyuki Uchino
Feb 6, 2002·The Journal of Biological Chemistry·Beata PyrzynskaBozena Kaminska
Mar 19, 2003·British Journal of Pharmacology·Alexa Klettner, Thomas Herdegen
Apr 5, 2003·Molecular and Cellular Neurosciences·Malgorzata Zawadzka, Bozena Kaminska

❮ Previous
Next ❯

Citations

Jul 2, 2009·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Kelley C LarsonMichael P Draper
Jul 19, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Malgorzata ZawadzkaBozena Kaminska
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Krishnan Sriram, James P O'Callaghan
May 24, 2008·Journal of Molecular Neuroscience : MN·Noelia FradejasSoledad Calvo
Sep 5, 2008·Nature Clinical Practice. Neurology·Kristopher T KahleDavid B Mount
Jan 1, 2008·Expert Review of Clinical Immunology·Bozena Kaminska, Karolina Swiatek-Machado
Mar 30, 2011·FEBS Letters·Djordje MiljkovićMarija Mostarica Stojković
Oct 12, 2014·Journal of Neuroimmunology·Ewelina RojewskaJoanna Mika
Jan 15, 2016·Molecular and Cellular Neurosciences·Dominika PilatJoanna Mika
Oct 7, 2008·Epilepsy & Behavior : E&B·Asla Pitkänen, Katarzyna Lukasiuk
Apr 24, 2007·Journal of Pediatric Surgery·Rafael RoeslerFelipe Dal Pizzol
Jul 21, 2009·The European Journal of Neuroscience·Galina DvoriantchikovaDmitry Ivanov
May 1, 2008·The European Journal of Neuroscience·José M Pérez-OrtizPedro Tranque
Jul 7, 2007·The European Journal of Neuroscience·Akihiko TaguchiTomohiro Matsuyama
Nov 2, 2006·Journal of Neurochemistry·Kinga SzydlowskaBozena Kaminska
May 17, 2008·CNS Neuroscience & Therapeutics·Germán Sierra-Paredes, Germán Sierra-Marcuño
May 8, 2013·Glia·Aleksandra Ellert-MiklaszewskaBozena Kaminska
Sep 4, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Stephan BrechtWolfram F Neiss
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Bozena KaminskaMaciej Lipko
Nov 11, 2006·Epilepsy Research·Zuzanna Setkowicz, Małgorzata Ciarach
Nov 18, 2006·European Journal of Pharmacology·Kinga SzydlowskaWojciech Danysz
Jul 21, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Klaudia KwiatkowskiJoanna Mika

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.