Background: Inflammation and excitotoxicity play important roles in the pathophysiology of ischemic brain damage. In previous studies we have shown a prolonged TNF-alpha (TNF-a) release, a long lasting high glutamate (glu) plasma concentration and an impaired platelet (plt) glu transport up to 3 months after the symptoms onset. Since high persisting plasmatic levels of TNF-a have been detected in stroke patients, we aimed to determine whether TNF-a administration could be sufficient to cause a defective plt glutamate uptake. Methods: Human blood plt were selected as a peripheral model of glutamate transport. 10 stroke patients and 20 control subjects were enrolled to test [H3]glu uptake after stimulation with increasing doses of TNF-a (10, 20 and 40ng/ml). Results: Plt from healthy subjects displayed a dose related reduction of glu uptake after TNF-a stimulation (total glu uptake decrease -35%). The reduction was less extensive in plt from stroke patients, possibly due to the demonstrated higher levels of plasmatic TNF-a in patients affected by stroke. Discussion: We showed that in-vitro administration of high concentration of TNF-a is able to effectively reduce glu uptake in human plt. The results suggest that the increase in plasmatic TNF-a in stroke patients may be responsible for the demonstrated reduction of plt glu uptake. Since decreased plt glu uptake could result in increased plasmatic glu levels, which in turn may generate a possible excitotoxic damage, pharmacological modulation of TNF-a levels might be helpful in the management of cerebrovascular patients.

Piazza, F., Longoni, M., Guerrato, I., Ferrarese, C. (2007). Effect of TNF-alpha on platelet glutamate uptake in Stroke patients. CEREBROVASCULAR DISEASES, 23(S2), 63-63.

Effect of TNF-alpha on platelet glutamate uptake in Stroke patients

Piazza, F;Longoni, M;Ferrarese, C
2007

Abstract

Background: Inflammation and excitotoxicity play important roles in the pathophysiology of ischemic brain damage. In previous studies we have shown a prolonged TNF-alpha (TNF-a) release, a long lasting high glutamate (glu) plasma concentration and an impaired platelet (plt) glu transport up to 3 months after the symptoms onset. Since high persisting plasmatic levels of TNF-a have been detected in stroke patients, we aimed to determine whether TNF-a administration could be sufficient to cause a defective plt glutamate uptake. Methods: Human blood plt were selected as a peripheral model of glutamate transport. 10 stroke patients and 20 control subjects were enrolled to test [H3]glu uptake after stimulation with increasing doses of TNF-a (10, 20 and 40ng/ml). Results: Plt from healthy subjects displayed a dose related reduction of glu uptake after TNF-a stimulation (total glu uptake decrease -35%). The reduction was less extensive in plt from stroke patients, possibly due to the demonstrated higher levels of plasmatic TNF-a in patients affected by stroke. Discussion: We showed that in-vitro administration of high concentration of TNF-a is able to effectively reduce glu uptake in human plt. The results suggest that the increase in plasmatic TNF-a in stroke patients may be responsible for the demonstrated reduction of plt glu uptake. Since decreased plt glu uptake could result in increased plasmatic glu levels, which in turn may generate a possible excitotoxic damage, pharmacological modulation of TNF-a levels might be helpful in the management of cerebrovascular patients.
Abstract in rivista
TNF-alpha, platelet, glutamate uptake, Stroke
English
2007
23
S2
63
63
S3
none
Piazza, F., Longoni, M., Guerrato, I., Ferrarese, C. (2007). Effect of TNF-alpha on platelet glutamate uptake in Stroke patients. CEREBROVASCULAR DISEASES, 23(S2), 63-63.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/32960
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