Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rat: therapeutic time window for FK506 in transient focal ischemia. 2001

T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
The Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. ariitaka@nms.ac.jp

Tacrolimus (FK506), an immunosuppressant currently used in clinic, is known to have neuroprotective properties. However, effects in focal ischemia are shown only in a endothelin induced middle cerebral artery (MCA) occlusion model or with filament technique at a relatively high dose. We have previously shown that FK506 had significant protective effects at a low dose of 0.3 mg kg(-1) when administered immediately after ischemia. In this study, we explored the therapeutic time window of FK506 at this low dose, in a transient focal ischemia model using filament technique. Male Sprague-Dawley rats were subjected to 2 h MCA occlusion and subsequent reperfusion. They received FK506 or vehicle (0.3 mg kg(-1)) i.v. at 30, 60 or 120 min after induction of ischemia, and were decapitated 24 h after ischemia. FK506 injected at 30 and 60 min significantly reduced cortical infarction volume (FK506 vs. vehicle; 30 min: 95 +/- 33 mm3 vs. 170 +/- 62 mm3, p < 0.05; 60 min: 93 +/- 45 mm3, vs. 168 +/- 35 mm3, p < 0.05, respectively). FK506 was ineffective when given at 120 min after ischemia. FK506 had no effect on edema formation, nor on the infarct volume in striatum. The therapeutic time window for this low dose of FK506 given i.v. is between 60 and 120 min in this model.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D001929 Brain Edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6) Brain Swelling,Cerebral Edema,Cytotoxic Brain Edema,Intracranial Edema,Vasogenic Cerebral Edema,Cerebral Edema, Cytotoxic,Cerebral Edema, Vasogenic,Cytotoxic Cerebral Edema,Vasogenic Brain Edema,Brain Edema, Cytotoxic,Brain Edema, Vasogenic,Brain Swellings,Cerebral Edemas, Vasogenic,Edema, Brain,Edema, Cerebral,Edema, Cytotoxic Brain,Edema, Cytotoxic Cerebral,Edema, Intracranial,Edema, Vasogenic Brain,Edema, Vasogenic Cerebral,Swelling, Brain
D002320 Cardiovascular Physiological Phenomena Processes and properties of the CARDIOVASCULAR SYSTEM as a whole or of any of its parts. Cardiovascular Physiologic Processes,Cardiovascular Physiological Processes,Cardiovascular Physiology,Cardiovascular Physiological Concepts,Cardiovascular Physiological Phenomenon,Cardiovascular Physiological Process,Physiology, Cardiovascular,Cardiovascular Physiological Concept,Cardiovascular Physiological Phenomenas,Concept, Cardiovascular Physiological,Concepts, Cardiovascular Physiological,Phenomena, Cardiovascular Physiological,Phenomenon, Cardiovascular Physiological,Physiologic Processes, Cardiovascular,Physiological Concept, Cardiovascular,Physiological Concepts, Cardiovascular,Physiological Phenomena, Cardiovascular,Physiological Phenomenon, Cardiovascular,Physiological Process, Cardiovascular,Physiological Processes, Cardiovascular,Process, Cardiovascular Physiological,Processes, Cardiovascular Physiologic,Processes, Cardiovascular Physiological
D002544 Cerebral Infarction The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction). Anterior Choroidal Artery Infarction,Cerebral Infarct,Infarction, Cerebral,Posterior Choroidal Artery Infarction,Subcortical Infarction,Cerebral Infarction, Left Hemisphere,Cerebral Infarction, Right Hemisphere,Cerebral, Left Hemisphere, Infarction,Cerebral, Right Hemisphere, Infarction,Infarction, Cerebral, Left Hemisphere,Infarction, Cerebral, Right Hemisphere,Infarction, Left Hemisphere, Cerebral,Infarction, Right Hemisphere, Cerebral,Left Hemisphere, Cerebral Infarction,Left Hemisphere, Infarction, Cerebral,Right Hemisphere, Cerebral Infarction,Right Hemisphere, Infarction, Cerebral,Cerebral Infarctions,Cerebral Infarcts,Infarct, Cerebral,Infarction, Subcortical,Infarctions, Cerebral,Infarctions, Subcortical,Infarcts, Cerebral,Subcortical Infarctions
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration

Related Publications

T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
December 2008, Chinese medical journal,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
March 1996, Neuroscience letters,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
January 1997, Neurobiology of disease,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
February 2002, Neuroreport,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
May 2004, Brain research,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
March 2003, Brain research,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
June 2011, Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
January 2010, Nitric oxide : biology and chemistry,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
June 2004, Magnetic resonance in medicine,
T Arii, and T Kamiya, and K Arii, and M Ueda, and C Nito, and K I Katsura, and Y Katayama
July 2004, British journal of pharmacology,
Copied contents to your clipboard!