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dead cells, developing an anti-inflammatory milieu
and generating pro-survival factors (14).
Microglial cells (monocytes) play a central role in
brain inflammation, and are essential for the mainte-
nance of integrity of the central nervous system (CNS).
Microglia cells are the first non-neuronal cells that
respond to injury, and they are the main source of pro-
inflammatory mediators. Furthermore, immediately
after acute events, such as stroke, blood-borne T and
B lymphocytes invade the CNS and stimulate resident
or infiltrating inflammatory cells, resulting in the deve-
lopment of inflammation. Through these interactions,
the brain’s precursor cells become activated and may
contribute to the healing process via the generation of
new cells to substitute for the neurones and glia that
have died due to stroke (15).
The latest reports suggest that inflammatory respon-
ses following injury to the CNS may not be entirely
negative, since they may also represent neuroinflam-
matory events occurring as reparative mechanisms
(16). Following brain trauma, a local remedial response
and deep remodelling (remodelling) to restore the
most important functions of the nervous tissue oc-
cur. As a result of damage to the CNS, the progenitor
cells of oligodendrocytes proliferate and differentiate
into mature oligodendrocyte cells that carry out re-
myelination processes, restoring the communication
between neurones (17).
Over recent decades, accumulating evidence sug-
gests that ELF-EMF has significant biological effects.
There is considerable evidence to show that exposure
to ELF-EMF can affect numerous biological functions,
both in vivo and in vitro, including DNA synthesis,
RNA transcription and gene expression (18), protein
synthesis, tissue repair, regulation of cell differentia-
tion (19) and cell proliferation (20). Exposure to ELF-
EMF can also modify the biophysical properties of cell
membranes, including their permeability to Ca 2+ ions
(21). Exposure to ELF-EMF reportedly modifies intra-
cellular Ca 2+ levels in rat thymic lymphocytes, human
T-lymphocytes, and Jurkat cells (22–24). Depending on
the dose (field induction and frequency) and duration
of treatment, and the type of inflamed tissue, exposure
to EMF can be harmful or may induce a cytoprotective
cellular response (25).
Many studies have shown that voltage-dependent
calcium channels may account for the biological ef-
fects of exposure to EMF. It has also been shown that
calcium channel blockers can greatly reduce the effects
of exposure to ELF-EMF, and cause interference in
cell differentiation and neurogenesis, with Ca 2+ influx
into cells (26). It is well documented that Ca 2+ ions af-
fect activity-dependent gene expression (27) and this
effect is mediated by signalling pathways activating
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Ca 2+ -responsive DNA regulatory elements, including
the transcription factor CREB, associated with cell
survival, neuronal differentiation, synaptic plasticity,
neurogenesis, and numerous other cell functions (28).
The potential use of electromagnetic field in stroke re-
habilitation was presented in study by Pena-Philippides
et al. (29). They tested the effect of pulsed electromag-
netic field (PEMF) on infarct size and inflammation
in a mouse model after cerebral ischaemia. This study
demonstrated that PEMF significantly influenced the
expression profile of pro- and anti-inflammatory factors
in the hemisphere ipsilateral to ischaemic damage (29).
A subsequent study in a human model was performed
by Capone et al., who showed that 1 mT ELF-EMF
reduced ischaemic lesion size in patients with acute
ischaemic stroke, which strongly suggested that ELF-
EMF could represent a potential therapeutic approach
after ischaemic stroke (30). Our previous study esti-
mated the clinical status of patients with the National
Institutes of Health Stroke Scale (NIHSS), Barthel Index
of Activities of Daily Living (ADL), modified Rankin
Scale (mRS), Mini-Mental State Examination (MMSE)
and Geriatric Depression Scale (GDS). Stroke-related
neurological deficit, estimated using NIHSS, decreased
approximately 65% more in the ELF-EMF group than
in the non-ELF-EMF group. mRS decreased in both
groups, but in the ELF-EMF group the reduction was
approximately 50% greater than in the non-ELF-EMF
group. Approximately 35% greater improvement in
cognitive impairment, as estimated by MMSE, was
observed after ELF-EMF treatment. Depressive syn-
drome, measured in GDS, decreased significantly, while
ΔGDS gained approximately 45% better results in the
ELF-EMF group than in the non-ELF-EMF group (9).
The regeneration of tissues depends on the course
of inflammation being controlled, so that the acute
inflammatory response does not become chronic. The
acute inflammatory condition allows the tissue to
regenerate through cell proliferation, while chronic
inflammation continuously destroys the tissue after
it has been repaired. Although drugs are commonly
used to suppress the inflammatory response, there is
evidence to show that suppressing inflammation can
hinder wound healing (31).
Although the delayed inflammatory response to
stroke induces secondary neurological injury, several
studies have shown that many cytokines can modulate
the expression of neurotrophins and their receptors,
which may indicate the involvement of inflamma-
tory mediators in neuroplasticity processes (32). In
light of this, we investigated whether exposure of
post-stroke patients to ELF-EMF affects expression
of pro-inflammatory cytokines (IL-1β, IL-2, INF-γ
and TGF-β). Among the pro-inflammatory cytokines