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Table 2 Overview of preclinical transcranial direct current stimulation (tDCS) studies

From: Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

References

Main focus

Impairment

Animal model

Stimulation protocol

Stimulation time frame

Yoon et al. [159]

Effects of anodal tDCS on behavioral and spatial memory in early stage TBI

Behavioral and spatial memory

36 male Sprague–Dawley rats, lateral FPI (moderate TBI), anesthetized during tDCS

Anodal tDCS, 0.2 mA, (2.82 mA/cm2 current density), for 20 min

Once per day, for 5 days, starting 1 or 2 weeks post-injury

Kim and Han [160]

Effects of anodal tDCS on neuroplasticity

Motor and sensory cortical excitability

31 male Sprague–Dawley rats (postnatal day 42), weight drop (175 g from 30 cm, 3 consecutive times, repetitive mild TBI), anesthetized during all procedures and evaluations

Anodal tDCS, 0.2 mA (0.255 mA/cm2 current density), for 30 min

Once, directly after TBI

Bragina et al. [161]

Perfusion and tissue oxygenation after anodal tDCS, motor and cognitive neurologic outcome

mCBF and tissue oxygenation, motor function

40 mice, CCI (5 m/s, 2 mm from cortical surface, mild to moderate TBI), awake during tDCS

Repetitive anodal tDCS, 0.1 mA, for 15 min

Over 4 weeks, for 4 consecutive days at 3-day intervals, starting 1 or 3 weeks post-injury

Yu et al. [162]

Effects of tDCS and ECS on motor and cognitive recovery, brain plasticity, spatial learning and memory

Motor and cognitive function

30 male Sprague–Dawley rats, weight drop (moderate TBI), awake during tDCS

Anodal tDCS, 0.1 mA, 50 Hz, 200 µs pulses, for 30 min

Once per day from days 3 to 28 after electrode positioning

Martens et al. [165]

Cathodal tDCS in the treatment of psychiatric-like symptoms after TBI

Impulsivity and attention

20 male Long-Evans rats, bilateral, frontal CCI (severe TBI), anesthetized during tDCS

Cathodal tDCS, 800 µA (0.708 mA/cm2), 10 min

Once per day for 7 days (2 h before testing), starting 6 weeks post-injury

Bragina et al. [164]

Effects of anodal tDCS on cerebrovascular reactivity and mCBF regulation

Cerebrovascular reactivity and mCBF

20 mice, CCI (5 m/s, 2 mm from cortical surface, mild to moderate TBI), awake during tDCS

Anodal tDCS, 0.1 mA, for 15 min

Once, 3 weeks post-injury

Park et al. [163]

Anodal tDCS to improve motor function after repetitive mild TBI

Motor function

65 male Sprague–Dawley rats, weight drop (175 g from 30 cm, once daily for 3 days, repetitive mTBI), anesthetized during tDCS

Anodal tDCS, 0.2 mA (0.255 mA/cm2), for 30 min

Once, 24 h after last induction of mTBI

References

Stimulus location

Tests

Acquired parameters

Persistent effects

Main findings

Yoon et al. [159]

Anode over perilesional area, cathode on chest

RRT, Barnes maze test, brain MRI, MRS, immunohistochemical analysis

Behavioral ability, spatial memory, lesion volume, brain edema, metabolites, BDNF expression

Beneficial effects visible 1 weeks after stimulation, no sustained effects after 3 weeks

tDCS increases recovery of spatial and memory functions when applied 2 weeks post injury, only improves spatial memory when applied 1 week post-injury

Kim and Han [160]

Anode around left motor cortex, counter electrode on thorax

MEP and SEP test, brain MRI, immunohistochemical analysis

Recovery of righting reflex, MEP latency and amplitude, SEP latency and amplitude, brain volumetric changes, GFAP expression

Immunohistochemistry performed 12 days after stimulation, showed no significant improvements

Single anodal tDCS after rmTBI induces early recovery of consciousness, increases modulation of cortical excitability and promotes transient motor recovery

Bragina et al. [161]

Anode near craniotomy, counter electrode on thorax

Custom-made LSCI, two-photon LSM, RRT, passive avoidance test, Y-maze test, Nissl staining

Regional and microvascular cerebral blood flow, motor deficits, learning, spatial and working memory

Preserved improvement in learning and motor abilities 1 week after stimulation was ended

Anodal tDCS increases brain microvascular blood flow and tissue oxygenation in TBI and sham mouse brain and could contribute to neurologic improvement

Yu et al. [162]

Anode above lesion, cathode at trunk

Rehabilitation training (SPRT, RRT, Y-maze), neurological examination, histology, immunohistochemistry

Success rate of SPRT and Y-maze tests, average rates of RRT, lesion assessments, c-Fos expression

Not investigated

ES with rehabilitation training for TBI rats is effective for motor recovery and brain plasticity, ECS induces faster behavioral and cognitive improvements than tDCS

Martens et al. [165]

Cathode near bregma, anode between scapulae

Five-choice serial reaction time task, analysis of brain slices to verify injury severity

Motor impulsivity, attention, relationship between magnitude of impairment and recovery

No lingering effects observed, disappeared after stimulation stopped

Relationship between magnitude of impulsive deficit and degree of tDCS-recovery, the most severely impaired subjects benefit the most from neuromodulation

Bragina et al. [164]

Anode near craniotomy, cathode on thorax

Two-photon LSM (before and after stimulation), cerebrovascular reactivity test (hypercapnia)

mCBF (arteriolar diameter), brain tissue oxygen flow (NADH autofluorescence)

Not investigated

Anodal tDCS restores cerebrovascular reactivity of parenchymal arterioles and regulation of mCBF, could contribute to neurologic improvement

Park et al. [163]

Anode over left M1 area, cathode on trunk

Brain MRI, histology, MEP evaluation (via TMS and needle electrodes), foot-fault test, rotarod test

Damage evaluation after repetitive mTBI, MEP amplitude and latency, motor coordination, sensorimotor function, balance alterations

Not investigated

Anodal tDCS at the M1 area after repetitive mTBI could improve MEP amplitude, balance control, postural orientation and motor endurance by activating the CST