Blood-Brain Barrier-Associated Proteins Are Elevated in Serum of Epilepsy Patients

Cells. 2023 Jan 19;12(3):368. doi: 10.3390/cells12030368.

Abstract

Blood-brain barrier (BBB) dysfunction emerges as one of the mechanisms underlying the induction of seizures and epileptogenesis. There is growing evidence that seizures also affect BBB, yet only scarce data is available regarding serum levels of BBB-associated proteins in chronic epilepsy. In this study, we aimed to assess serum levels of molecules associated with BBB in patients with epilepsy in the interictal period. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 100 patients who were seizure-free for a minimum of seven days and analyzed by ELISA. The results were compared with an age- and sex-matched control group. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B were higher in patients with epilepsy in comparison to control group (p < 0.0001; <0.0001; 0.001; <0.0001; <0.0001, respectively). Levels of CCL-2, ICAM-1, P-selectin and TSP-2 did not differ between the two groups. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B are elevated in patients with epilepsy in the interictal period, which suggests chronic processes of BBB disruption and restoration. The pathological process initiating epilepsy, in addition to seizures, is probably the factor contributing to the elevation of serum levels of the examined molecules.

Keywords: ECM; MMP-2; MMP-9; S100B; TIMP-1; TIMP-2; blood–brain barrier; epilepsy; inflammation; seizure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier
  • Epilepsy*
  • Humans
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • P-Selectin
  • Seizures
  • Tissue Inhibitor of Metalloproteinase-1*
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • P-Selectin
  • Intercellular Adhesion Molecule-1

Grants and funding

The analyses performed for this study were financed by an internal grant financed from the Institute of Psychiatry and Neurology under project number 501-15-021-20016 within statutory activity. No additional external funding and support was received for this study.