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.
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.
Leroy
Claire
C
INSERM U.398, Faculty of Medicine, 11 rue Humann, 67085 Strasbourg, Cedex, France. leroy@neurochem.u-strasbg.fr
Roch
Catherine
C
Koning
Estelle
E
Namer
Izzie J
IJ
Nehlig
Astrid
A
D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001810:Blood Volume; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008094:Lithium; D008297:Male; D009474:Neurons / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley
D010862:Pilocarpine; D008094:Lithium