Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients

Abstract

Background: Neuroplasticity ensures the improvement of functional status in patients after stroke. The aim of this study was to evaluate the effect of extremely low-frequency electromagnetic field therapy (ELF-EMF) on brain plasticity in the rehabilitation of patients after stroke. Methods: Forty-eight patients were divided into two groups underwent the same rehabilitation program, but in the study group, the patients additionally were exposed to a standard series of 10 ELF-EMF treatments. To determine the level of neuroplasticity, we measured the plasma level of the brain-derived neurotrophic factor (BDNF), the vascular-endothelial growth factor, as well as BDNF mRNA expression. Additionally, we determined the molecule levels for hepatocyte growth factor, stem cell factor, stromal cell-derived factor 1α, nerve growth factor β, and leukemia inhibitory factor, using 5plex cytokine panel in plasma. After 4 weeks, during which patients had undergone neurorehabilitation and neurological examinations, we assessed functional recovery using the Barthel Index, Mini-Mental State Examination (MMSE), Geriatric Depression Scale, National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS). Results: We observed that ELF-EMF significantly increased growth factors and cytokine levels involved in neuroplasticity, as well as promoted an enhancement of functional recovery in post-stroke patients. Additionally, we presented evidence that these effects could be related to the increase of gene expression on the mRNA level. Moreover, a change of BDNF plasma level was positively correlated with the Barthel Index, MMSE, and negatively correlated with GDS. Conclusion: Extremely low-frequency electromagnetic field therapy improves the effectiveness of rehabilitation of post-stroke patients by improving neuroplasticity processes.

Keywords: brain-derived neurotrophic factor; extremely low-frequency electromagnetic field; neuroplasticity; rehabilitation; stroke.

FIGURE 1

Comparison of the BDNF level obtained from the ELF-EMF group vs. the non-ELF-EMF group. (A) BDNF plasma concentration. Statistical significance between ELF-EMF and non-ELF-EMF groups: b vs. d: p < 0.0001. (B) BDNF mRNA expression. Statistical significance between ELF-EMF and non-ELF-EMF groups: b vs. d: p < 0.0001.

FIGURE 2

Comparison of the plasma VEGF level obtained from the ELF-EMF group vs. the non-ELF-EMF group. Statistical significance between ELF-EMF and non-ELF-EMF groups: b vs. d: p < 0.001.

FIGURE 3

Comparison of the plasma cytokine profile obtained from the ELF-EMF group vs the non-ELF-EMF group. (A) HGF plasma level. Statistical significance between ELF-EMF and non-ELF-EMF groups: b vs. d: p < 0.01. (B) SCF plasma level. Statistical significance between ELF-EMF and non-ELF-EMF groups: b vs. d: p < 0.05. (C) SDF-1α plasma level.

FIGURE 4

Clinical parameters NIHSS, ADL, mRS, MMSE, and GDS as measured in the study vs. the control group. Data is shown here as a delta of scores obtained before and after the standard series of treatments (Δ NIHSS = the decline of NIHSS; ΔADL = the gain of ADL; Δ mRS = the decline of mRS; Δ MMSE = the gain of MMSE; Δ GDS = the decline of GDS).

FIGURE 5

Scatterplots presenting correlation between changes of BDNF plasma level (in pg/ml) in ELF-EMF group and (A) changes of ADL; (B) changes of MMSE; (C) changes of GDS.