Abstract:We demonstrate here for the first time the mechanism by which combined therapy using TMS and EE after TBI leads to functional improvement, possibly via cortical excitability and reorganization.
“…In recent years, rTMS has evolved into an effective method for basic neuroscience research,as well as useful clinical treatment 14,15. rTMS can be utilized in the treatment of depression, dementia, Parkinson’s disease, migraine, and multiple sclerosis by altering neuronal excitability, neurotransmitter, and peptides metabolism, and immune function 16–18.…”
Background:
The mechanism of action of repetitive transcranial magnetic stimulation (rTMS) involves the generation of neuronal and action potentials utilizing induced currents in time-varying magnetic fields. However, the long-lasting and effective biological impact of magnetic stimulation does not appear to be completely explained by the transient magnetic field pulses. In this context, we hypothesized magnetic stimulation may affect the expression of iron-containing enzymes in neurons, mediating the long-lasting biological effects associated with this stimulus.
Methods:
Primarily cultured hippocampus neurons from SD rats were used as the cell model in this study. These were randomly divided into control, sham, and magnetic stimulation groups to probe into the effect of the magnetic field directly. The latter group received 40%, 60%, and 100% maximal stimulator output Tesla (1.68, 2.52, and 4.2 T) with low-frequency rTMS (1 Hz). The expression of iron-containing enzymes (catalase and aconitase) and non-ferrous enzymes (protein kinase A) was measured with Western blotting and ELISA.
Results:
The survival rates of neurons in the 40%T and 60%T groups were significantly increased in comparison to the controls (
P
<0.05), while those in the 100%T group showed cell damage, with slightly disturbed neurite connections and decreased survival rate. Furthermore, catalase and aconitase expression was higher in all of the stimulated groups in comparison to controls (
P
<0.05). On the other hand, the expression of the iron-containing enzymes decreased in the 100%T group in comparison with the 40%T and 60%T groups (
P
<0.05). Meanwhile, the expression of protein kinase A was not significantly increased in the groups which underwent magnetic stimulation.
Conclusion:
rTMS may increase the expression of ferrous enzymes but does not have a strong effect on non-ferrous enzymes. Excessive intensity of magnetic stimulation may reduce neuronal survival rate and affect the expression of iron-containing enzymes. The mechanism underlying the lasting effect of rTMS may be related to the increase of ferriferous expression induced by magnetic stimulation, with a clear correlation with stimulation intensity.
“…In recent years, rTMS has evolved into an effective method for basic neuroscience research,as well as useful clinical treatment 14,15. rTMS can be utilized in the treatment of depression, dementia, Parkinson’s disease, migraine, and multiple sclerosis by altering neuronal excitability, neurotransmitter, and peptides metabolism, and immune function 16–18.…”
Background:
The mechanism of action of repetitive transcranial magnetic stimulation (rTMS) involves the generation of neuronal and action potentials utilizing induced currents in time-varying magnetic fields. However, the long-lasting and effective biological impact of magnetic stimulation does not appear to be completely explained by the transient magnetic field pulses. In this context, we hypothesized magnetic stimulation may affect the expression of iron-containing enzymes in neurons, mediating the long-lasting biological effects associated with this stimulus.
Methods:
Primarily cultured hippocampus neurons from SD rats were used as the cell model in this study. These were randomly divided into control, sham, and magnetic stimulation groups to probe into the effect of the magnetic field directly. The latter group received 40%, 60%, and 100% maximal stimulator output Tesla (1.68, 2.52, and 4.2 T) with low-frequency rTMS (1 Hz). The expression of iron-containing enzymes (catalase and aconitase) and non-ferrous enzymes (protein kinase A) was measured with Western blotting and ELISA.
Results:
The survival rates of neurons in the 40%T and 60%T groups were significantly increased in comparison to the controls (
P
<0.05), while those in the 100%T group showed cell damage, with slightly disturbed neurite connections and decreased survival rate. Furthermore, catalase and aconitase expression was higher in all of the stimulated groups in comparison to controls (
P
<0.05). On the other hand, the expression of the iron-containing enzymes decreased in the 100%T group in comparison with the 40%T and 60%T groups (
P
<0.05). Meanwhile, the expression of protein kinase A was not significantly increased in the groups which underwent magnetic stimulation.
Conclusion:
rTMS may increase the expression of ferrous enzymes but does not have a strong effect on non-ferrous enzymes. Excessive intensity of magnetic stimulation may reduce neuronal survival rate and affect the expression of iron-containing enzymes. The mechanism underlying the lasting effect of rTMS may be related to the increase of ferriferous expression induced by magnetic stimulation, with a clear correlation with stimulation intensity.
“…Electromagnetic induction generates currents that are capable of stimulating neurons within the specific region. Since non-invasive stimulation of the brain reduces the risks encountered in surgical patients, such as hemorrhage, infection, and the overall cost of the procedure, TMS has recently gained interest for use in functional and behavioral research as well as rehabilitation research after brain injury (Ferbert et al, 1992;Celnik et al, 2009;Lu et al, 2015;Shin et al, 2018;Krishnan et al, 2019).…”
“…The result of rTMS is affected by the intensity and frequency of the stimulation: low frequency rTMS (≤1 Hz) and high frequency rTMS (≥5 Hz) decrease and increase the cortical excitability, respectively (Ridding and Ziemann, 2010). rTMS has been reported to treat many neurological diseases including traumatic brain injury, spinal cord injury (SCI), neurodegenerative disorders, schizophrenia, and substance addiction (Tazoe and Perez, 2015;Benussi et al, 2018;Shin et al, 2018). The therapeutic effect induced by rTMS might be associated to several processes, such as increased neural stem and progenitor cell growth and neuronal differentiation, release of neurotrophic factors (e.g., brain-derived neurotrophic factor, BDNF), and regulation of neuronal excitability and cerebral blood flow (Lee et al, 2015).…”
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that uses electromagnetic fields to stimulate the brain. rTMS can restore an impaired central nervous system and promote proliferation of neural stem/progenitor cells (NSPCs), but optimal stimulus parameters and mechanisms underlying these effects remain elusive. The purpose of this study is to investigate the effect of different rTMS stimulus parameters on proliferation and apoptosis of spinal cord-derived NSPCs, the expression of brain-derived neurotrophic factor (BDNF) after rTMS, and the potentially underlying pathways. NSPCs were isolated from mice spinal cord and stimulated by different frequencies (1/10/20 Hz), intensities (0.87/1.24/1.58 T), and number of pulses (400/800/1,500/3,000) once a day for five consecutive days. NSPC proliferation was analyzed by measuring the neurosphere diameter and Brdu staining, apoptosis was detected by cell death enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and NSPC viability was assessed by cell counting kit-8 assay. We found that specific parameters of frequency (1/10/20 Hz), intensity (1.24/1.58 T), and number of pulses (800/1,500/3,000) promote proliferation and apoptosis (p < 0.05 for all), but 20 Hz, 1.58 T, and 1,500 pulses achieved the optimal response for the NSPC viability. In addition, rTMS significantly promoted the expression of BDNF at the mRNA and protein level, while also increasing Akt phosphorylation (Thr308 and Ser473; p < 0.05). Overall, we identified the most appropriate rTMS parameters for further studies on NSPCs in vitro and in vivo. Furthermore, the effect of magnetic stimulation on NSPC proliferation might be correlated to BDNF/Akt signaling pathway.
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