Short-Term Cortical Electrical Stimulation during the Acute Stage of Traumatic Brain Injury Improves Functional Recovery

Abstract

Functional restoration is an important issue in the treatment of traumatic brain injury (TBI). Various electrical stimulation devices and protocols have been applied in preclinical studies and have shown therapeutic potential for brain trauma. Short-term invasive cortical electrical stimulation during the acute stage of TBI might be a feasible adjuvant therapy for patients with moderate-to-severe brain injury receiving neurosurgical treatment in the intensive care unit. However, the therapeutic effects of short-term multisession cortical electrical stimulation for brain trauma are not clear. This study explored the therapeutic effects of acute-stage short-term cortical electrical stimulation on TBI. We conducted seven sessions of one-hour cortical electrical stimulation from day 0 to day 6 in rats after brain trauma by controlled cortical impact and then evaluated the functional outcome and histopathological changes. Our data showed that short-term cortical electrical stimulation improved motor coordination, short-term memory, and learning ability and attenuated neurological severity after brain trauma. Lesion volume, apoptosis, and gliosis after brain trauma were reduced, and trauma-induced neurogenesis in the hippocampus for the innate neural reparative response was increased. Our study demonstrated that short-term cortical electrical stimulation applied in the acute stage of traumatic brain injury is a potential adjuvant therapy to improve the recovery of neurological deficits.

Inhibition of Voltage-Gated Na+ Currents Exerted by KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea), an Inhibitor of Na+-Ca2+ Exchanging Process

“…There is growing evidence to show that a significant fraction of subthreshold or background Na + currents is functionally active in varying types of excitable cells [ 20 , 22 , 24 , 27 , 57 , 58 , 59 , 60 , 61 ]. Recent investigations have also demonstrated possible modifications of sinusoidal voltage wave on membrane ionic currents [ 62 , 63 , 64 , 65 ]. For these reasons, efforts were further given to answer the question of whether I Na(P) can be susceptible to adjustments by sinusoidal voltage waveform or whether or how sinusoidal voltage-induced I Na(P) can be perturbed by adding KB-R7943.…”

Intracranial Neuromodulation for Neurologic Recovery

“…Yoon et al9 reported significant improvement in motor control in rats with moderate to severe TBI but no major effects in coordination or balance. However, other animal studies have demonstrated that TBI treated with MCS confers marked improvement in spatial memory, sensorimotor function, and motor coordination 1,10,11. These studies did not use the same behavioral tests to quantify motor abilities but demonstrated that cortical stimulation promotes motor recovery after TBI.…”

“…However, other animal studies have demonstrated that TBI treated with MCS confers marked improvement in spatial memory, sensorimotor function, and motor coordination. 1,10,11 These studies did not use the same behavioral tests to quantify motor abilities but demonstrated that cortical stimulation promotes motor recovery after TBI. It would be beneficial to obtain more consistent data if there was consensus on which tests more accurately measure functional recovery.…”

Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single‐nucleus RNA sequencing

“…The use of electrical brain stimulation (EBS) as a therapeutic modality for treatment of brain disorders has evolved significantly, with recent developments pushing pathway activation, etc., to treat Parkinson's disease (PD), Alzheimer's disease (AD), and other central nervous system (CNS) disorders. [6][7][8][9][10][11][12][13][14] Take treatment for AD as an example, studies have suggested that the use of 40 Hz flicker stimulation can modulate abnormal gamma oscillations in the brain waves of AD model mice to some extent, thereby improving impaired learning and memory functions. [15][16][17] However, the latest research refutes this finding, claiming that flicker stimulation cannot regulate gamma oscillations in brain waves, nor can it reduce excessive Aβ deposition in the brains of AD mice or ameliorate AD symptoms.…”

“…The use of electrical brain stimulation (EBS) as a therapeutic modality for treatment of brain disorders has evolved significantly, with recent developments pushing the boundaries of our understanding and treatment capabilities 1–6 . The principle of this approach is to use precisely applied electrical currents to modulate neuronal activity, such as neuronal membrane stability and action potential, ion and neurotransmitter fluxes, intracellular pathway activation, etc., to treat Parkinson's disease (PD), Alzheimer's disease (AD), and other central nervous system (CNS) disorders 6–14 …”