Abstract
Cerebral ischemia initiates an inflammatory response in the brain that is associated with the induction of a variety of cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha/beta (IL-1alpha/beta) that contributes to stroke injury. Transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR) resulted in significant increases in TNF-alpha and IL-1beta levels. We have previously demonstrated up-regulation of secretory phospholipase A2 IIA (sPLA2 IIA) mRNA and protein expression, increased PLA2 activity, and loss of phosphatidylcholine after 1-h tMCAO and 24-h reperfusion in SHR. Treatment with TNF-alpha antibody or IL-1 receptor antagonist significantly attenuated infarction volume, sPLA2 IIA protein expression, PLA2 activity and significantly restored phosphatidylcholine levels after tMCAO. This suggests that cytokine induction up-regulates sPLA2 IIA protein expression, resulting in altered lipid metabolism that contributes to stroke injury.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Animals
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Antibodies / pharmacology
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Cerebral Infarction / enzymology*
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Cerebral Infarction / immunology
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Cerebral Infarction / physiopathology
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Cytokines / antagonists & inhibitors
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Cytokines / immunology
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Cytokines / metabolism*
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Encephalitis / enzymology*
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Encephalitis / immunology
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Encephalitis / physiopathology
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Enzyme Activation / drug effects
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Enzyme Activation / immunology
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Group II Phospholipases A2
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Infarction, Middle Cerebral Artery / immunology
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Infarction, Middle Cerebral Artery / metabolism
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Infarction, Middle Cerebral Artery / physiopathology
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Interleukin 1 Receptor Antagonist Protein / pharmacology
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Interleukin-1alpha / antagonists & inhibitors
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Interleukin-1alpha / immunology
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Interleukin-1alpha / metabolism
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Ischemic Attack, Transient / enzymology*
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Ischemic Attack, Transient / immunology
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Ischemic Attack, Transient / physiopathology
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Male
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Membrane Lipids / metabolism
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Nerve Degeneration / drug therapy
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Nerve Degeneration / enzymology
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Nerve Degeneration / immunology
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Phosphatidylcholines / metabolism
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Phospholipases A / genetics
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Phospholipases A / metabolism*
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Phospholipases A2
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Rats
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Rats, Inbred SHR
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation / drug effects
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Up-Regulation / immunology*
Substances
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Antibodies
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Cytokines
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1alpha
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Interleukin-1beta
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Membrane Lipids
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Phosphatidylcholines
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Tumor Necrosis Factor-alpha
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Phospholipases A
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Group II Phospholipases A2
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Phospholipases A2