Levetiracetam decreases the seizure activity and blood-brain barrier permeability in pentylenetetrazole-kindled rats with cortical dysplasia.
This study investigates the effects of levetiracetam (LEV) on the functional and structural properties of blood-brain barrier (BBB) in pentylenetetrazole (PTZ)-kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. In offsprings, kindling was induced by giving subconvulsive doses of PTZ three times per week for 45 days. While all kindled rats with CD died during epileptic seizures evoked by the administration of a convulsive dose of PTZ in 15 to 25 min, one week LEV (80 mg/kg) pretreatment decreased the mortality to 38% in the same setting. LEV caused a remarkable decrease (p<0.01) in extravasation of sodium fluorescein dye into the brain tissue of kindled animals with CD treated with convulsive dose of PTZ. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Immunoreactivity for glial fibrillary acidic protein (GFAP) was observed to be slightly increased by acute convulsive challenge in kindled rats with CD while LEV pretreatment led to GFAP immunoreactivity comparable to that of controls. An increased c-fos immunoreactivity in kindled rats with CD exposed to convulsive PTZ challenge was also observed with LEV pretreatment. Tight junctions were ultrastructurally intact, whereas LEV decreased the increased pinocytotic activity in brain endothelium of kindled rats with CD treated with convulsive dose of PTZ. The present study showed that LEV decreased the increased BBB permeability considerably by diminishing vesicular transport in epileptic seizures induced by convulsive PTZ challenge in kindled animals with CD.
Gurses
Candan
C
Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Turkey. candan.gurses@gmail.com
Ekizoglu
Oguzhan
O
Orhan
Nurcan
N
Ustek
Duran
D
Arican
Nadir
N
Ahishali
Bulent
B
Elmas
Imdat
I
Kucuk
Mutlu
M
Bilgic
Bilge
B
Kemikler
Gonul
G
Kalayci
Rivaze
R
Karadeniz
Ahmet
A
Kaya
Mehmet
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects*; D004727:Endothelium / Q000187:drug effects; D019793:Fluorescein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000077287:Levetiracetam; D054220:Malformations of Cortical Development / Q000150:complications*; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010433:Pentylenetetrazole; D010873:Pinocytosis / Q000187:drug effects; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure
D000927:Anticonvulsants; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D016760:Proto-Oncogene Proteins c-fos; D000077287:Levetiracetam; D019793:Fluorescein; D010433:Pentylenetetrazole; D010889:Piracetam