TY - JOUR
T1 - Expression of adhesion factors induced by epileptiform activity in the endothelium of the isolated guinea pig brain in vitro
AU - Librizzi, Laura
AU - Regondi, Maria Cristina
AU - Pastori, Chiara
AU - Frigerio, Simona
AU - Frassoni, Carolina
AU - De Curtis, Marco
PY - 2007/4
Y1 - 2007/4
N2 - Purpose: Brain inflammation has been recently considered in the pathogenesis of focal epilepsies. Synthesis of pro-inflammatory mediators in the brain was described both in experimental models of seizures and in human postsurgical tissue. Inflammatory mediators may up-regulate endothelial adhesion molecules, therefore promoting adhesion and homing of leucocytes into the brain. In the present study, expression of inducible adhesion factors in brain endothelium was verified after pharmacological induction of seizure-like activity in specific brain areas of the in vitro isolated guinea pig brain. Methods: Experiments were performed in isolated guinea-pig brains maintained in vitro by arterial perfusion. In this preparation, brief application of the GABAa receptor-antagonist, bicuculline, consistently induced focal ictal discharges in the limbic region that secondarily diffuse to the neocortex, as verified by simultaneous electrophysiological recording of extracellular activity. At the end of the electrophysiological experiment (after 5 h in vitro), brains were fixed and immunostaining for adhesion molecules P-selectin and ICAM-1 and for Fos protein was evaluated. Results: Immunohistochemical analysis of isolated brains in which seizure-like activity was induced revealed expression of inducible adhesion factors P-selectin and ICAM-1 in the endothelium of small-medium size brain vessels. In particular, the expression of these molecules was consistently observed in all areas involved in epileptic seizure-like ictal activity (limbic cortices and neocortex), and was infrequently found in regions that generated interictal spiking (piriform cortex), suggesting a trigger role played by seizures for endothelial activation. An increase in Fos protein expression was evident in all analyzed limbic areas and in the neocortex, indicating a correlation between the areas of neuronal and endothelial activation. In control brains maintained in vitro for comparable times without induction of epileptiform activity, no immunoreactivity for Fos and adhesion molecules was observed. Conclusions: Seizure-like activity in an in vitro isolated brain preparation induces the expression of adhesion molecules in the cerebral endothelium. These observations indicate that local endothelial activation may represent a crucial step for the development of an inflammatory response induced by seizures, and suggest a possible novel pathogenic mechanism during the process of epileptogenesis.
AB - Purpose: Brain inflammation has been recently considered in the pathogenesis of focal epilepsies. Synthesis of pro-inflammatory mediators in the brain was described both in experimental models of seizures and in human postsurgical tissue. Inflammatory mediators may up-regulate endothelial adhesion molecules, therefore promoting adhesion and homing of leucocytes into the brain. In the present study, expression of inducible adhesion factors in brain endothelium was verified after pharmacological induction of seizure-like activity in specific brain areas of the in vitro isolated guinea pig brain. Methods: Experiments were performed in isolated guinea-pig brains maintained in vitro by arterial perfusion. In this preparation, brief application of the GABAa receptor-antagonist, bicuculline, consistently induced focal ictal discharges in the limbic region that secondarily diffuse to the neocortex, as verified by simultaneous electrophysiological recording of extracellular activity. At the end of the electrophysiological experiment (after 5 h in vitro), brains were fixed and immunostaining for adhesion molecules P-selectin and ICAM-1 and for Fos protein was evaluated. Results: Immunohistochemical analysis of isolated brains in which seizure-like activity was induced revealed expression of inducible adhesion factors P-selectin and ICAM-1 in the endothelium of small-medium size brain vessels. In particular, the expression of these molecules was consistently observed in all areas involved in epileptic seizure-like ictal activity (limbic cortices and neocortex), and was infrequently found in regions that generated interictal spiking (piriform cortex), suggesting a trigger role played by seizures for endothelial activation. An increase in Fos protein expression was evident in all analyzed limbic areas and in the neocortex, indicating a correlation between the areas of neuronal and endothelial activation. In control brains maintained in vitro for comparable times without induction of epileptiform activity, no immunoreactivity for Fos and adhesion molecules was observed. Conclusions: Seizure-like activity in an in vitro isolated brain preparation induces the expression of adhesion molecules in the cerebral endothelium. These observations indicate that local endothelial activation may represent a crucial step for the development of an inflammatory response induced by seizures, and suggest a possible novel pathogenic mechanism during the process of epileptogenesis.
KW - Fos
KW - ICAM-1
KW - Isolated guinea pig brain in vitro
KW - P-selectin
KW - Seizures
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UR - http://www.scopus.com/inward/citedby.url?scp=34247176722&partnerID=8YFLogxK
U2 - 10.1111/j.1528-1167.2007.01047.x
DO - 10.1111/j.1528-1167.2007.01047.x
M3 - Article
C2 - 17386052
AN - SCOPUS:34247176722
VL - 48
SP - 743
EP - 751
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 4
ER -