References | Main focus | Impairment | Animal model | Stimulation protocol | Stimulation time frame |
---|---|---|---|---|---|
Yoon YS et al. [138] | Effects of rTMS and EES on TBI | Motor function | 51 male Sprague–Dawley rats (21 died from TBI), Marmarou’s weight drop (450 g from 1 m, diffuse, mild TBI, medial impact), awake and immobilized during TMS | 90% of max. device output, 10 Hz, 3 s stim and 6 s pause, for 10 min | Twice per day, day 1–14 post-injury |
Yoon KJ et al. [152] | rTMS for behavioral recovery | Motor function, brain metabolism, cell death | 20 adult male Sprague–Dawley rats, lateral FPI (3.5–4 atm pressure, severe TBI), awake and immobilized during TMS | 80% of RMT, 10 Hz, 15 trains of 2 s, 1 s inter-train interval | 10 sessions over 2 weeks, beginning on 4th day post-injury |
Lu H et al. [153] | rTMS for pediatric TBI | Motor function | 26 juvenile Sprague–Dawley rats, CCI over left primary somatosensory cortex (severity unclear), TMS under 2% isoflurane | 25% of max. device output, 20 Hz, 9 trains of 100 pulses, 55 s inter-train interval, for 9 min | Twice per week, starting 9 post-injury, for 4 weeks |
Lu X et al. [156] | rTMS for neuromodulation and neurogenesis | Loss of brain parenchyma, reduced brain metabolism, neurological impairment | 38 adult Sprague–Dawley rats, Feeney’s weight drop (moderate TBI, right hemisphere), awake and immobilized during TMS | 60% of max. device output, 5 Hz, 36 trains of 25 pulses, 15 s inter-train interval, 900 pulses/day, figure-of-eight coil | From 2 days post-injury until 1 day before sacrificed (7/14/28 days after TBI) |
Verdugo-Diaz et al. [157] | Treatment with intermediate frequency rTMS | Mortality, general behavioral changes | 97 male Wistar rats, Marmarou’s weight drop (motor cortex, severe TBI), awake and immobilized during TMS (animals trained for immobilization) | 50% of max. device output (120% of RMT), 2 Hz, 15 min per day, figure-of-eight coil | Starting 1 day post-injury, for 7 consecutive days |
Shin et al. [154] | Therapy with rTMS and environmental enrichment | motor function | 97 male Sprague–Dawley rats, CCI (4 m/s, moderate TBI, right hemisphere), MEP assessment under isoflurane, electrophysiological recordings under urethane, fMRI under sedation, rTMS under 2% isoflurane | 10 Hz, 7 cycles of 4 s, 26 s between cycles, figure-of-eight coil, (stim. intensity unclear) | Starting 1 day post-injury, daily, for 6 days |
Sekar et al. [155] | Low-field magnetic stimulation (LFMS, rTMS variant) treatment after TBI | Cognitive and motor functions | 48 male C57BL/6 mice, weight drop (60Â g from 1Â m, closed head trauma, repetitive TBI, once daily for 3 consecutive days, severity unclear), awake and immobilized during TMS | 40Â Hz, 6Â ms pulses, 80 trains of 2Â s, 8Â s pause, magn. field changes between uniform and linear gradient every 2Â min, for 20Â min | Once per day, following recovery from rightening reflex after TBI, for 3Â days and once on day 4 |
Qian et al. [158] | Investigation of cellular mechanisms caused by rTMS treatment | General overview | 45 male Sprague–Dawley rats, Feeney's weight drop (20 g × 30 cm impact force, moderate TBI), awake and immobilized during rTMS | 30% of motor threshold, 40 Hz, 40 trains of 1 s, in 15 s intervals | Starting 4 days post-injury, once daily, for 2 weeks, five times per week |
References | Stimulus location | Tests | Acquired parameters | Persistent effects | Main findings |
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Yoon YS et al. [138] | Center of the coil placed above injury site | Limb placement test, SPRT, RRT, immunohistochemistry | Limb placement changes, SPRT success rate, RRT performance time rate, c-Fos expression | Not investigated | TMS and EES resulted in significant improvement in SPRT and accelerated improvement in RRT, with particularly robust effects of EES |
Yoon KJ et al. [152] | Area with largest MEP amplitude at the weaker biceps femoris after suprathreshold stim., side not stated (probably ipsilateral) | Rotarod and beam balance tests, brain MRI, magnetic resonance spectroscopy, western blot, immunohistochemistry | Motor coordination, balance ability, intact and lesioned hemispheric volume, brain metabolism, apoptotic signaling | Not investigated | rTMS did not have beneficial effects on motor recovery, enhancement of anti-apoptotic response in perilesional area |
Lu H et al. [153] | Contralateral primary sensory region | Extracellular electrophysiological recordings, fMRI, open field test, forelimb and hindlimb reflex test, immunostaining | CaMKII expression (LTP), MUA responses, LFP magnitude, evoked fMRI cortical responses, behavioral tests (physiology and hyperactivity) | Long-lasting increase of excitability in non-injured cortex after 4Â weeks of TMS therapy | Significant increases in evoked-fMRI cortical response, evoked synaptic activity, evoked neuronal firing and expression of neuroplasticity markers, decreased hyperactivity in behavioral tests |
Lu X et al. [156] | Whole brain influenced by magnetic field (max. stim. over the center of the brain) | Behavioral tests (mNSS evaluation), hematoxylin and eosin staining, immunohistochemistry, PET examination | Behavioral recovery, relative brain parenchyma loss, cell proliferation and neurogenesis, neuron protection, cell apoptosis, metabolic activity | Not investigated | High-frequency rTMS may decrease mortality, mature neuron loss, apoptosis, improve behavioral recovery, cell proliferation and neurogenesis in the SVZ, metabolic activity in the contralateral site was not affected |
Verdugo-Diaz et al. [157] | Injury site | Hunter’s 21-point behavioral-neurological scale, histology | Body weight, food intake, post-TBI bleeding and mortality, neurobehavioral score, cellular morphological changes, disruptions in hippocampal tissue architecture | Not investigated | Movement restriction prevents damage caused by TBI, intermediate-frequency rTMS slightly promotes behavioral and histologic recovery after TBI |
Shin et al. [154] | Midpoint between lambda and bregma, medial located | Beam walk and challenge ladder tests, electrophysiology, evoked LFP, MEP assessment, fMRI in the contralateral cortex | Beam traversal latency, mean speed and slips from ladder, MEP amplitude, LFP magnitude, fMRI activation maps | Combination of EE and TMS led to benefits in sensorimotor function lasting up to 6Â weeks | Combined therapy with TMS and EE after TBI leads to functional improvements, possibly via cortical excitability and reorganization, long-term effects probably due to EE rather than TMS |
Sekar et al. [155] | Cortical and subcortical areas | RRT, open field test, novel location recognition test, immunohistochemistry, western blot | Time on rotarod, locomotor activity, cognitive function, PrPc level in plasma, GFAP, NeuN and PrPc protein levels, CLOCK and CRY2 levels | Not investigated | LFMS treatment improved motor and cognitive function in mice after repetitive TBI, restored PrPc level, decreased proteins associated with circadian rhythm, decreased GFAP levels, increased NeuN levels, and showed neuroprotective effects |
Qian et al. [158] | Coil placed above ipsilateral side, close to the scalp | mNSS assessment, TEM, immunohistochemistry, western blot, RT-PCR detection | Injury severity, synaptic ultrastructure, protein expression (BDNF, TrkB, NMDAR1, P-CREB, SYN), mRNA expression levels | Not investigated | rTMS may promote recovery of neurological functions in TBI rats through enhanced SYN protein levels to promote synaptic reconstruction and affecting the expression of proteins related to LTP occurrence |