title: Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels.
abstract: BACKGROUND
  Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures.
  
  
  METHODS
  Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability.
  
  
  RESULTS
  We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients.
  
  
  CONCLUSIONS
  Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xi'an Medical University, No, 48, West Fenghao Road, Xi'an 710077, Shaanxi Province, China. liyajun9@hotmail.com
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Li
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhe
authors.forename: Ming-Jue
authors.initials: MJ
authors.lastname: Wang
authors.forename: Shao-Ting
authors.initials: ST
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Xiang-Li
authors.initials: XL
authors.lastname: Kong
authors.forename: Xing
authors.initials: X
authors.lastname: Zuo
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000473:pathology*; D002452:Cell Count; D004569:Electroencephalography; D004830:Epilepsy, Tonic-Clonic / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010539:Permeability; D012640:Seizures / Q000134:cerebrospinal fluid* / Q000473:pathology*; D012709:Serum Albumin / Q000032:analysis; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D012709:Serum Albumin; D020780:Matrix Metalloproteinase 9