Abstract
BackgroundRepetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism.ObjectivesTo investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis.MethodsPoststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels.ResultsTwo-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism.ConclusionsThe combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.
Highlights
Stroke is the leading cause of death and the main cause of long-term disability worldwide
Repetitive transcranial magnetic stimulation can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. repetitive transcranial magnetic stimulation (rTMS) seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by Brain-derived neurotrophic factor (BDNF) gene polymorphism
Serum BDNF and matrix metalloproteinase-9 (MMP-9) levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in Wolf Motor Function (WMFT) (ρ = -0.422, p = 0.002)
Summary
Stroke is the leading cause of death and the main cause of long-term disability worldwide. It is reported that rTMS increases blood BDNF (mature BDNF + proBDNF) levels in patients with depression [10,11]. Val66met polymorphism of the BDNF gene negatively influences the effect of rTMS on poststroke upper limb hemiparesis [13]. These findings suggest that the observed changes in peripheral blood are due to rTMS-induced modulation of BDNF-TrkB signaling in the brain [12]. Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. RTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism.
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