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

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.

Meta-analysis of MMP-9 levels in the serum of patients with epilepsy

“…These included studies were published and peer reviewed. All 13 studies were case–control ( Zhang and Hao, 2009 ; Zhang et al, 2013 ; Cudna et al, 2017 ; Bronisz et al, 2018 ; Meguid et al, 2018 ; El Moneam Abdallah et al, 2019 ; Wang, 2019 ; Zhang, 2019 ; Huang et al, 2020 ; Li et al, 2020 ; Tao et al, 2020 ; Bronisz et al, 2023 ; Cudna et al, 2023 ) studies. Enzyme-linked immunoassay is a unified method for MMP-9 detection.…”

“…Since only 8 out of the 13 papers had complete total MMP-9 data, we conducted a random-effects meta-analysis of the 8 studies that were included and performed to generate forest plots ( Bronisz et al, 2018 ; Meguid et al, 2018 ; El Moneam Abdallah et al, 2019 ; Wang, 2019 ; Huang et al, 2020 ; Li et al, 2020 ; Tao et al, 2020 ; Bronisz et al, 2023 ). The remaining 5 papers were used for subgroup analysis.…”

Nano‐delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives

“… Increased permeability: The BBB in epilepsy is more permeable than the normal BBB, allowing for the passage of larger molecules and cells that would normally be excluded from the brain. This increased permeability is thought to be due to a number of factors, including inflammation, oxidative stress, and changes in the tight junctions that line the cerebral capillaries 11 Altered expression of transporters: The BBB in epilepsy also has altered expression of transporters, which are proteins that help regulate molecules' movement across the BBB.…”

“…This increased permeability is thought to be due to a number of factors, including inflammation, oxidative stress, and changes in the tight junctions that line the cerebral capillaries. 11 Altered expression of transporters: The BBB in epilepsy also has altered expression of transporters, which are proteins that help regulate molecules' movement across the BBB. This altered expression can lead to imbalances in the levels of certain nutrients and chemicals in the brain, which can contribute to seizures.…”

“…This increased permeability is thought to be due to a number of factors, including inflammation, oxidative stress, and changes in the tight junctions that line the cerebral capillaries. 11 …”