Blood-brain barrier damage, but not parenchymal white blood cells, is a hallmark of seizure activity.
It has long been held that chronic seizures cause blood-brain barrier (BBB) damage. Recent studies have also demonstrated that BBB damage triggers seizures. We have used the BBB osmotic disruption procedure (BBBD) to examine the correlation between BBB opening, pattern of white blood cell (WBCs) entry into the brain and seizure occurrence. These findings were compared to results from resected epileptic brain tissue from temporal lobe epilepsy (TLE) patients. We confirmed that a successful BBB osmotic opening (BBBD) leads to the occurrence of acute epileptiform discharges. Electroencephalography (EEG) and time-joint frequency analysis reveal EEG slowing followed by an increase in the 10-20Hz frequency range. Using green fluorescent protein (GFP)-labeled WBCs (GFP-WBCs) suspended in Evans Blue we found that, at time of BBB-induced epileptiform discharges, WBCs populated the perivascular space of a leaky BBB. Similar results were obtained at time of pilocarpine seizure. No frank WBCs extravasation in the brain parenchyma was observed. In TLE brain specimens, CD45-positive leukocytes were detected only in the vascular and perivascular spaces while albumin and IgG extravasates were parenchymal. The pattern was similar to those observed in rats. Our data suggest that neither acute-induced nor chronic seizures correlate with WBC brain parenchymal migration while albumin and IgG brain leakage is a hallmark of acute and chronic seizures.
Marchi
Nicola
N
Department of Cell Biology, Cleveland Clinic, Cleveland, OH 44195, USA.
Teng
Qingshan
Q
Ghosh
Chaitali
C
Fan
Qingyuan
Q
Nguyen
Minh T
MT
Desai
Nirav K
NK
Bawa
Harpreet
H
Rasmussen
Peter
P
Masaryk
Thomas K
TK
Janigro
Damir
D
D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002675:Child, Preschool; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000503:physiopathology; D005070:Evans Blue; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D014162:Transfection / Q000379:methods
D000418:Albumins; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D005070:Evans Blue; D017493:Leukocyte Common Antigens