Preclinical Validation of Electrodes for Single Anodal Transcranial Direct Current Stimulation on Rat Model With Chronic Stress-Induced Depression

Transcranial direct current stimulation (tDCS) is an effective and safe noninvasive brain stimulation (NIBS) procedure to modulate neuronal excitability. The present preclinical study was carried out to validate the impact of the innovative high definition (HD) fabricated spiking Au/AgCl electrodes via a noninvasive tDCS procedure on a rat model with depression-like behavior. In this study, a chronic stress-induced depression-like behavior rat model was developed over a period of 14 days. Furthermore, the aftereffects of NIBS procedures were investigated by providing a tDCS dose ( ${2.00} \text {mA} \times {5.00} \text {min}$ ) by placing the electrodes on the interested region of the rat brain. This study was performed in healthy rats, control rats with depression-like behavior, and tDCS treated rats, which were used to examine the differential aftereffects of tDCS dose. After single tDCS dose, a significant increase in average band power of electroencephalogram (EEG) has been observed ( $\text {F}{(}{2},{15}{)} = {8.376}; {P} = {0.0036}$ ) alongside a significant increase in the glutamate level of hippocampus (HPC; $\text {F}{(}{2},\!{15}{)} = {8.919}; {P} = {0.0028}$ ), a significant reduction in immobility time ( $\text {F}{(}{2},{15}{)} = {7.552}; {P} = {0.0054}$ ), and a significant increase in the percentage sucrose intake has been observed ( $\text {F}{(}{2}, {15}{)} = {5.941}; {P} = {0.0126}$ ). In addition, immunohistochemistry (IHC) showed a significant increase in the Iba1 protein expression in microglia cell in the both cortex and HPC region ( ${P} < {0.05}$ ). Hence, the fabricated electrodes can deliver a tDCS dose that can penetrate up to the cortex and HPC regions from the surface of brain noninvasively within tolerable and safety limits.

I. Introduction

Depressive disorders are one of the leading causes of disability [1], and chronic stress reported to be major contributors [2]. Excessive stress related events contribute toward depression-like behavior, which causes alteration in the brain structures, neurochemistry, and functions [3]. Depression-like behaviors cause imbalance of neuronal circuitry, which involves a change in the behavioral state [4]. Repetitive ignorance in the change in the behavioral state due to chronic stress leads to cognitive impairment, which can also involve losing the functional ability of memory and learning [4]. Furthermore, chronic stress-induced depression-like behavior imbalances the functionality of neurotransmitters. The previous studies reported deficits in serotonin or 5-hydroxytryptamine (5-HT) in stress and depression [5]. Furthermore, stress and depression were reported to disturb the function of -aminobutyric acid (GABA)-inhibitory and glutamate-excitatory neurotransmitters, which play a responsible role to control and exchange for neural circuit level information [6]. The previous brain imaging studies have observed functional and structural change in depression [7]. The microglial cells play an important role in controlling the glutamate level in the pathological conditions, which leads to neuronal survival or damage [8]. The key role of microglia-ramified cells is to provide surveillance to the neurons for external damage. Highly ramified microglia cells were seen in normal condition, but in the chronic stress condition, microglia cells lose their ramification and become amoeboid [3], [9]. Preclinical studies have observed some evidence related to decrease in the population of the neurons and number of microglia cells in stress and depression [9], [10]. Various researches are being carried out related to development of efficient precautionary and therapeutic procedures for mental disorders in various fields, such as physical medicine, pharmacology, biomedical and neural engineering, psychology and behavior, and many more [11], [12]. Several research works are being carried out to develop noninvasive, low cost portable, and easy to use neurorehabilitation, which can help to improve the lifestyle of patients and reduce the burden on caregivers [13].