Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy
Abstract
:1. Introduction
2. Results
2.1. BDNF
2.2. NSE
2.3. S100B
2.4. VILIP-1
3. Discussion
Limitations
4. Materials and Methods
4.1. Patients
4.2. Sampling Procedures
4.3. Biochemical Analysis
4.4. Immunohistochemical (IHC) Analysis
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ATP | adenosine triphosphate |
a.u. | arbitrary units |
BBB | blood–brain barrier |
BDNF | brain-derived neurotrophic factor |
CNS | central nervous system |
CSF | cerebrospinal fluid |
DAPI | 4′,6-diamidino-2-phenylindole (a marker of a cell nucleus) |
EEG | electroencephalography |
GDNF | glial-cell-line-derived neurotrophic factor |
HG | hippocampal gliosis |
HS | hippocampal sclerosis |
IHC | immunohistochemical analysis |
IL | interleukin |
ILAE | International League Against Epilepsy |
MRI | magnetic resonance imaging |
MTLE | mesial temporal lobe epilepsy |
NMDA | N-methyl-D-aspartate |
n.s. | not significant |
NSE | neuron-specific enolase |
PBMCs | peripheral blood mononuclear cells |
PBS | phosphate-buffered saline |
S100B | S100 calcium-binding protein B |
TBI | traumatic brain injury |
VILIP-1 | visinin-like protein 1 |
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Analyte | Type of Analysis/Tissue | ||||
---|---|---|---|---|---|
Biochemical Analysis | IHC Analysis | ||||
Hippocampus (pg/mg of Protein) | Blood | Hippocampus (a.u.) | Blood | ||
Serum (pg/mL) | PBMCs (pg/mg of Protein) | PBMCs (a.u.) | |||
BDNF | 224.8 (138.0; 361.1) (N = 38) | 3458.7 (2707.6; 3891.9) (N = 41) | 1243.2 (623.2; 2169.8) (N = 40) | 0.027 (0.017; 0.037) (N = 43) | 3.222 (2.14; 3.811) (N = 43) |
NSE | 4077.3 (2593.0; 5722.2) (N = 40) | 1.8 (1.2; 2.8) (N = 40) | 67.1 (33.1; 154.3) (N = 40) | 0.0095 (0.0064; 0.0148) (N = 43) | 3.749 (3.163; 5.163) (N = 42) |
VILIP-1 | 98.6 (65.4; 190.4) (N = 39) | 244.72 (155.1; 371.3) (N = 41) | 124.9 (81.0; 228.9) (N = 39) | - | - |
S100B | 2298.3 (1800.4; 2942.5) (N = 39) | 38.5 (23.5; 66.5) (N = 41) | 1.55 (0.44; 4.85) (N = 39) | 0.011 (0.008; 0.015) (N = 30) | 1.842 (1.401; 2.274) (N = 30) |
Parameter | Type of Analysis/Tissue | ||||
---|---|---|---|---|---|
Biochemical Analysis | IHC Analysis | ||||
Hippocampus | Blood | Hippocampus | Blood | ||
Serum | PBMCs | PBMCs | |||
Correlation between blood and hippocampal levels | - | rho = −0.11 (n.s., N = 38) | rho = −0.17 (n.s., N = 38) | - | rho = 0.15 (n.s., N = 43) |
BDNF levels in female (f) vs. male (m) patients | f vs. m (Z = 1.08, n.s., N = 38) | f vs. m (Z = 1.22, n.s., N = 40) | f vs. m (Z = 1.12, n.s., N = 40) | f vs. m (t = 0.36, n.s., N = 43) | f vs. m (Z = 0.97, n.s., N = 43) |
Correlation between BDNF levels and age (years) | rho = −0.18 (n.s., N = 38) | r = 0.32 (p = 0.045, N = 41) | rho = 0.05 (n.s., N = 40) | r = −0.12 (n.s., N = 43) | rho = 0.13 (n.s., N = 43) |
Correlation between BDNF levels and disease duration (years) | rho = −0.19 (n.s., N = 38) | r = 0.09 (n.s., N = 41) | rho = 0.09 (n.s., N = 40) | r = 0.17 (n.s., N = 43) | rho = −0.08 (n.s., N = 43) |
Correlation between BDNF levels and average seizure frequency per month | rho = 0.15 (n.s., N = 38) | rho = 0.17 (n.s., N = 41) | rho = 0.46, p < 0.003 (N = 40) | rho = −0.06 (n.s., N = 43) | rho = 0.18 (n.s., N = 43) |
Correlation between BDNF levels and average seizure duration (s) | rho = −0.17 (n.s., N = 38) | rho = −0.003 (n.s., N = 41) | rho = 0.01 (n.s., N = 40) | rho = −0.06 (n.s., N = 43) | rho = 0.001 (n.s., N = 43) |
BDNF levels in patients with hippocampal sclerosis (HS) vs. hippocampal gliosis (HG) | HS [0.23 ± 0.03 ng/mL] vs. HG [0.25 ± 0.01 ng/mL] (F(1, 36) < 1, N = 38) | HS [3.52 (2.80; 3.84) ng/mL] vs. HG [3.07 (2.53; 3.99) ng/mL] (Z = 0.73, p > 0.05, N = 41) | HS [1.48 (0.84; 2.49) ng/mL] vs. HG [1.03 (0.58; 1.59) ng/mL] (Z = 1.59, p = 0.11, N = 40) | HS [0.03 ± 0.003 a.u.] vs. HG [0.024 ± 0.003 a.u.] (F(1, 41) = 2.2, p = 0.15, N = 43) | HS [3.67 (2.79; 4.01) a.u.] vs. HG [2.3 (1.47; 3.33) a.u.] (Z = 2.87, p = 0.0041, N = 43) |
Outcome (ILAE classes) | F(5, 32) = 1.7, p > 0.05, N = 38 | F(5, 35) < 1, N = 41 | H(5, N = 40) = 9.53, p = 0.09 | F(5, 37) < 1, N = 43 | H(5, N = 43) = 6.12, p > 0.05 |
BDNF levels in patients who were treated with drugs stimulating GABAergic activity (1) vs. those who were not (0) | 1 vs. 0 (t = −0.03, n.s., N = 38) | 1 vs. 0 (t = 0.77, n.s., N = 41) | 1 vs. 0 (Z = 1.00, n.s., N = 40) | 1 vs. 0 (t = 0.2, n.s., N = 43) | 1 vs. 0 (Z = −1.06, n.s., N = 43) |
BDNF levels in patients who were treated with drugs regulating ion channel activity (1) vs. those who were not (0) | 1 vs. 0 (Z = −0.21, n.s., N = 38) | 1 vs. 0 (t = 2.70, p = 0.01, N = 41) | 1 vs. 0 (Z = 0.84, n.s., N = 40) | 1 vs. 0 (t = −0.13, n.s., N = 43) | 1 vs. 0 (Z = −0.37, n.s., N = 43) |
BDNF levels in patients who were treated with drugs inhibiting the activity of NMDA receptors (1) vs. those who were not (0) | 1 vs. 0 (t =−0.23, n.s., N = 38) | 1 vs. 0 (t =−0.61, n.s., N = 41) | 1 vs. 0 (Z = 0.35, n.s., N = 40) | 1 vs. 0 (t = −0.05, n.s., N = 43) | 1 vs. 0 (Z = −0.41, n.s., N = 43) |
Parameter | Type of Analysis/Tissue | ||||
---|---|---|---|---|---|
Biochemical Analysis | IHC Analysis | ||||
Hippocampus | Blood | Hippocampus | Blood | ||
Serum | PBMCs | PBMCs | |||
Correlation between blood and hippocampal levels | - | rho = −0.29 (p = 0.06, N = 40) | rho = 0.55 (p < 0.001, N = 40) | - | rho = 0.3 (p = 0.057, N = 41) |
NSE levels in female (f) vs. male (m) patients | f vs. m (t = −0.05, n.s., N = 40) | f vs. m (Z = −1.95, p = 0.05, N = 40) | f vs. m (Z = −0.14, n.s., N = 40) | f vs. m (Z = −1.68, n.s., N = 43) | f vs. m (Z = −0.68, n.s., N = 42) |
Correlation between NSE levels and age (years) | r = −0.18 (n.s., N = 40) | rho = 0.10 (n.s., N = 40) | rho = −0.27 (n.s., N = 40) | rho = −0.08 (n.s., N = 43) | rho = 0.17 (n.s., N = 42) |
Correlation between NSE levels and disease duration (years) | rho = −0.04 (n.s., N = 40) | rho = 0.05 (n.s., N = 40) | rho = −0.19 (n.s., N = 40) | rho = 0.04 (n.s., N = 43) | rho = −0.08 (n.s., N = 42) |
Correlation between NSE levels and average seizure frequency per month | rho = 0.05 (n.s., N = 40) | rho = 0.03 (n.s., N = 40) | rho = 0.02 (n.s., N = 40) | rho = −0.09 (n.s., N = 43) | rho = 0.07 (n.s., N = 42) |
Correlation between NSE levels and average seizure duration (s) | rho = −0.00 (n.s., N = 40) | rho = −0.06 (n.s., N = 40) | rho = −0.11 (n.s., N = 40) | rho = −0.09 (n.s., N = 42) | rho = 0.34 (p = 0.03, N = 41) |
NSE levels in patients with hippocampal sclerosis (HS) vs. hippocampal gliosis (HG) | HS vs. HG (t = −1.33, n.s., N = 40) | HS vs. HG (Z = 0.97, n.s., N = 40) | HS vs. HG (Z = −1.92, n.s., N = 40) | HS vs. HG (Z = −0.43, n.s., N = 43) | HS vs. HG (Z = 0.87, n.s., N = 42) |
Outcome (ILAE classes) | F(5, 33) = 0.19, p > 0.05 | H(5, N = 39) = 4.23, p > 0.05 | H(5, N = 39) = 5.22, p > 0.05 | H(5, N = 43) = 2.92, p > 0.05 | H(5, N = 42) = 6.79, p > 0.05 |
NSE levels in patients who were treated with drugs stimulating GABAergic activity (1) vs. those who were not (0) | 1 vs. 0 (t = 0.23, p = 0.056, N = 40) | 1 vs. 0 (Z = −0.17, n.s., N = 40) | 1 vs. 0 (Z = 1.67, n.s., N = 40) | 1 vs. 0 (Z = 0.23, n.s., N = 43) | 1 vs. 0 (Z = 0.52, n.s., N = 42) |
NSE levels in patients who were treated with drugs regulating ion channel activity (1) vs. those who were not (0) | 1 vs. 0 (t = −0.52, n.s., N = 40) | 1 vs. 0 (Z = 1.00, n.s., N = 40) | 1 vs. 0 (Z = 0.82, n.s., N = 40) | 1 vs. 0 (Z = 1.5, n.s., N = 43) | 1 vs. 0 (Z = 1.86, n.s., N = 42) |
NSE levels in patients who were treated with drugs inhibiting the activity of NMDA receptors (1) vs. those who were not (0) | 1 vs. 0 (t = 2.17, p < 0.05, N = 40) | 1 vs. 0 (Z = −2.52, p < 0.05, N = 40) | 1 vs. 0 (Z = 0.08, n.s., N = 40) | 1 vs. 0 (Z = −1.65, n.s., N = 43) | 1 vs. 0 (Z = −0.68, n.s., N = 42) |
Parameter | Type of Analysis/Tissue | ||||
---|---|---|---|---|---|
Biochemical Analysis | IHC Analysis | ||||
Hippocampus | Blood | Hippocampus | Blood | ||
Serum | PBMCs | PBMCs | |||
Correlation between blood and hippocampal levels | - | rho = 0.14 (n.s., N = 39) | rho = 0.21 (n.s., N = 39) | - | r = 0.16 (n.s., N = 30) |
S100B levels in female (f) vs. male (m) patients | f vs. m (t = 1.85, p = 0.07, N = 39) | f vs. m (Z = 0.86, n.s., N = 41) | f vs. m (Z = 0.43, n.s., N = 39) | f vs. m (t = −0.17, n.s., N = 30) | f vs. m (t = −0.45, n.s., N = 30) |
Correlation between S100B levels and age (years) | r = −0.06 (n.s., N = 39) | rho = 0.34, (p < 0.05, N = 41) | rho = 0.06 (n.s., N = 39) | r = −0.05 (n.s., N = 30) | r = −0.12 (n.s., N = 30) |
Correlation between S100B levels and disease duration (years) | r = −0.23 (n.s., N = 39) | rho = 0.19 (n.s., N = 41) | rho = 0.10 (n.s., N = 39) | r = 0.16 (n.s., N = 30) | r = −0.22 (n.s., N = 30) |
Correlation between S100B levels and average seizure frequency per month | rho = 0.26 (n.s., N = 39) | rho = 0.23 (n.s., N = 41) | rho = 0.27 (n.s., N = 39) | rho = −0.14 (n.s., N = 30) | rho = 0.004 (n.s., N = 30) |
Correlation between S100B levels and average seizure duration (s) | rho = −0.05 (n.s., N = 39) | rho = 0.02 (n.s., N = 41) | rho = 0.05 (n.s., N = 39) | rho = −0.06 (n.s., N = 29) | rho = 0.28 (n.s., N = 29) |
S100B levels in patients with hippocampal sclerosis (HS) vs. hippocampal gliosis (HG) | HS vs. HG (t = −0.20, n.s., N = 39) | HS vs. HG (Z = 1.39, n.s., N = 41) | HS vs. HG (Z = −0.12, n.s., N = 39) | HS vs. HG (t = −0.91, n.s., N = 30) | HS vs. HG (t = −1.31, n.s., N = 30) |
Outcome (ILAE classes) | F(5, 33) = 0.30, p > 0.05, N = 39 | H(5, N = 41) = 5.62, n.s. | H(5, N = 39) = 2.19, n.s. | F(5, 24) =1.04, p > 0.05 | F(5, 24) = 1.46, p > 0.05 |
S100B levels in patients who were treated with drugs stimulating GABAergic activity (1) vs. those who were not (0) | 1 vs. 0 (t = −1.08, n.s., N = 39) | 1 vs. 0 (Z = 0.64, n.s., N = 41) | 1 vs. 0 (Z = −0.09, n.s., N = 39) | 1 vs. 0 (t = 1.58, n.s., N = 30) | 1 vs. 0 (t = 0.43, n.s., N = 30) |
S100B levels in patients who were treated with drugs regulating ion channel activity (1) vs. those who were not (0) | 1 vs. 0 (t = −0.92, n.s., N = 39) | 1 vs. 0 (Z = 0.85, n.s., N = 41) | 1 vs. 0 (Z = −0.76, n.s., N = 39) | 1 vs. 0 (t = −0.42, n.s., N = 30) | 1 vs. 0 (t = 0.42, n.s., N = 42) |
S100B levels in patients who were treated with drugs inhibiting the activity of NMDA receptors (1) vs. those who were not (0) | 1 vs. 0 (t = 1.44, n.s., N = 39) | 1 vs. 0 (Z = −0.12, n.s., N = 41) | 1 vs. 0 (Z = 0.08, n.s., N = 39) | 1 vs. 0 (t = 1.61, n.s., N = 30) | 1 vs. 0 (t = −0.66, n.s., N = 30) |
Biochemical Analysis | |||
---|---|---|---|
Parameter | Tissue | ||
Hippocampus | Blood | ||
Serum | PBMCs | ||
Correlation between blood and hippocampal levels | - | rho = 0.11 (n.s., N = 39) | rho = 0.01 (n.s., N = 39) |
VILIP-1 levels in female (f) vs. male (m) patients | f vs. m (Z = 1.93, p = 0.054, N = 39) | f vs. m (Z = −1.03, n.s., N = 41) | f vs. m (Z = −0.49, n.s., N = 39) |
Correlation between VILIP-1 levels and age (years) | rho = 0.09 (n.s., N = 39) | rho = 0.10 (n.s., N = 41) | rho = −0.26 (n.s., N = 39) |
Correlation between VILIP-1 levels and disease duration (years) | rho = 0.05 (n.s., N = 39) | rho = 0.01 (n.s., N = 41) | rho = −0.07 (n.s., N = 39) |
Correlation between VILIP-1 levels and average seizure frequency per month | rho = 0.24 (n.s., N = 39) | rho = 0.10 (n.s., N = 41) | rho = 0.10 (n.s., N = 39) |
Correlation between VILIP-1 levels and average seizure duration (s) | rho = −0.03 (n.s., N = 39) | rho = −0.05 (n.s., N = 41) | rho = −0.23 (n.s., N = 39) |
VILIP-1 levels in patients with hippocampal sclerosis (HS) vs. hippocampal gliosis (HG) | HS vs. HG (Z = 1.93, n.s., N = 39) | HS vs. HG (Z = 0.95, n.s., N = 41) | HS vs. HG (Z = −1.13, n.s., N = 39) |
Outcome (ILAE classes) | H(5, N = 39) = 3.27, n.s. | H(5, N = 41) = 1.13, n.s. | H(5, N = 39) = 4.38, n.s. |
VILIP-1 levels in patients who were treated with drugs stimulating GABAergic activity (1) vs. those who were not (0) | 1 vs. 0 (Z = −0.25, n.s., N = 39) | 1 vs. 0 (Z = −0.74, n.s., N = 41) | 1 vs. 0 (Z = 0.64, n.s., N = 39) |
VILIP-1 levels in patients who were treated with drugs regulating ion channel activity (1) vs. those who were not (0) | 1 vs. 0 (Z = −0.98, n.s., N = 39) | 1 vs. 0 (Z = −0.30, n.s., N = 41) | 1 vs. 0 (Z = −0.71, n.s., N = 39) |
VILIP-1 levels in patients who were treated with drugs inhibiting the activity of NMDA receptors (1) vs. those who were not (0) | 1 vs. 0 (Z = 1.45, n.s., N = 39) | 1 vs. 0 (Z = −1.88, p = 0.06, N = 41) | 1 vs. 0 (Z = 0.39, n.s., N = 39) |
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Tikhonova, M.A.; Shvaikovskaya, A.A.; Zhanaeva, S.Y.; Moysak, G.I.; Akopyan, A.A.; Rzaev, J.A.; Danilenko, K.V.; Aftanas, L.I. Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy. Int. J. Mol. Sci. 2024, 25, 502. https://doi.org/10.3390/ijms25010502
Tikhonova MA, Shvaikovskaya AA, Zhanaeva SY, Moysak GI, Akopyan AA, Rzaev JA, Danilenko KV, Aftanas LI. Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy. International Journal of Molecular Sciences. 2024; 25(1):502. https://doi.org/10.3390/ijms25010502
Chicago/Turabian StyleTikhonova, Maria A., Anna A. Shvaikovskaya, Svetlana Y. Zhanaeva, Galina I. Moysak, Anna A. Akopyan, Jamil A. Rzaev, Konstantin V. Danilenko, and Lyubomir I. Aftanas. 2024. "Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy" International Journal of Molecular Sciences 25, no. 1: 502. https://doi.org/10.3390/ijms25010502