10.3389/fneur.2019.00382.s002
Natália Ferreira Mendes
Natália Ferreira
Mendes
Aline Priscila Pansani
Aline Priscila
Pansani
Elis Regina Ferreira Carmanhães
Elis Regina Ferreira
Carmanhães
Poliana Tange
Poliana
Tange
Juliana Vieira Meireles
Juliana Vieira
Meireles
Mayara Ochikubo
Mayara
Ochikubo
Jair Ribeiro Chagas
Jair Ribeiro
Chagas
Alexandre Valotta da Silva
Alexandre Valotta
da Silva
Glaucia Monteiro de Castro
Glaucia Monteiro
de Castro
Luciana Le Sueur-Maluf
Luciana
Le Sueur-Maluf
Image_2_The Blood-Brain Barrier Breakdown During Acute Phase of the Pilocarpine Model of Epilepsy Is Dynamic and Time-Dependent.jpg
Frontiers
2019
epilepsy
blood-brain barrier
pilocarpine
status epilepticus
Evans blue
sodium fluorescein
2019-06-10 14:50:51
Figure
https://frontiersin.figshare.com/articles/figure/Image_2_The_Blood-Brain_Barrier_Breakdown_During_Acute_Phase_of_the_Pilocarpine_Model_of_Epilepsy_Is_Dynamic_and_Time-Dependent_jpg/8248610
<p>The maintenance of blood-brain barrier (BBB) integrity is essential for providing a suitable environment for nervous tissue function. BBB disruption is involved in many central nervous system diseases, including epilepsy. Evidence demonstrates that BBB breakdown may induce epileptic seizures, and conversely, seizure-induced BBB disruption may cause further epileptic episodes. This study was conducted based on the premise that the impairment of brain tissue during the triggering event may determine the organization and functioning of the brain during epileptogenesis, and that BBB may have a key role in this process. Our purpose was to investigate in rats the relationship between pilocarpine-induced status epilepticus (SE), and BBB integrity by determining the time course of the BBB opening and its subsequent recovery during the acute phase of the pilocarpine model. BBB integrity was assessed by quantitative and morphological methods, using sodium fluorescein and Evans blue (EB) dyes as markers of the increased permeability to micromolecules and macromolecules, respectively. Different time-points of the pilocarpine model were analyzed: 30 min after pilocarpine injection and then 1, 5, and 24 h after the SE onset. Our results show that BBB breakdown is a dynamic phenomenon and time-dependent, i.e., it happens at specific time-points of the acute phase of pilocarpine model of epilepsy, recovering in part its integrity afterwards. Pilocarpine-induced changes on brain tissue initially increases the BBB permeability to micromolecules, and subsequently, around 5 h after SE, the BBB breakdown to macromolecules occurs. After BBB breakdown, EB dye is captured by damaged cells, especially neurons, astrocytes, and oligodendrocytes. Although the BBB permeability to macromolecules is restored 24 h after the start of SE, the leakage of micromolecules persists and the consequences of BBB degradation are widely disseminated in the brain. Our findings reveal the existence of a temporal window of BBB dysfunction in the acute phase of the pilocarpine model that is important for the development of therapeutic strategies that could prevent the epileptogenesis.</p>