In the lithium-pilocarpine model of epilepsy, brain lesions are not linked to changes in blood-brain barrier permeability: an autoradiographic study in adult and developing rats.
Fiche publication
Date publication
août 2003
Journal
Experimental neurology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NAMER Izzie-Jacques
Tous les auteurs :
Leroy C, Roch C, Koning E, Namer IJ, Nehlig A
Lien Pubmed
Résumé
Lithium-pilocarpine-induced status epilepticus (SE) leads to the genesis of massive neuronal loss in adult rats and to a lesser extent in P21 rats. Neuronal damage occurs mainly via a process of necrosis in limbic forebrain, cerebral cortex, thalamus, and substantia nigra. It is not known, however, whether damage is the result of local excitotoxic hyperactivity or if leakage at the blood-brain barrier (BBB) could participate in the damaging process. Therefore, we investigated the permeability of the BBB in adult and P21 rats using [alpha-(14)C]aminoisobutyric acid, which does not cross an intact BBB, at 90 min after the onset of SE. At both ages, BBB opening occurred both in structures that will undergo damage (thalamus, septum, amygdala) and structures that will not be injured (globus pallidus, hypothalamus). In addition, neuronal damage occurs in the absence of increased BBB permeability in hippocampus, entorhinal cortex, and substantia nigra. Moreover, the increase in the intensity and distribution of BBB permeability changes is age-related, suggesting a differential activation of seizure circuits in adult and P21 rats. In summary, there is no clear correlation between the anatomical distribution of BBB opening and the occurrence of neuronal damage which, in this model, appears to rather depend on excitotoxic mechanisms due to major neuronal hyperexcitability.
Mots clés
Age Factors, Animals, Autoradiography, Behavior, Animal, drug effects, Blood Volume, Blood-Brain Barrier, drug effects, Brain, blood supply, Disease Models, Animal, Epilepsy, chemically induced, Lithium, Male, Neurons, pathology, Permeability, drug effects, Pilocarpine, Rats, Rats, Sprague-Dawley
Référence
Exp. Neurol.. 2003 Aug;182(2):361-72