Transcranial Direct Current Stimulation Ameliorates Cognitive Impairment via Modulating Oxidative Stress, Inflammation, and Autophagy in a Rat Model of Vascular Dementia

Abstract

To investigate the potential applications and the molecular mechanisms of transcranial direct current stimulation (tDCS) on cognitive impairment in a vascular dementia (VD) animal model. Sprague-Dawley rats were used in this study. VD rat model was induced by modified permanent bilateral common carotid artery occlusion (2-VO) approach. Anodal tDCS was applied to the animals. Morris water maze was used to analyze spatial memory and navigation ability. The pathological changes in the hippocampal CA1 region and cerebral cortex were examined via Hematoxylin-Eosin staining. The rats were sacrificed for the measurement of the level of superoxide (SOD), glutathione (GSH), reactive oxidative species (ROS), malondialdehyd (MDA), Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α level in the hippocampus. Western blot was carried out to measure the hippocampal expression of microtubule-associated protein 1 light chain 3 (LC-3) and p62. Rats with VD have decreased number of neurons in the hippocampus and cerebral cortex, as well as worse cognitive impairment. The proliferation of activated microglia and astroglia, accompanied with attenuation of myelination were observed in the white matter about 1 month after 2-VO operation. These abnormalities were significantly ameliorated by tDCS treatment. Further study revealed that anodal tDCS could suppress the MDA and ROS level, while enhance the SOD and GSH level to reduce the oxidative stress. Anodal tDCS could inhibit hypoperfusion-induced IL-1β, IL-6, and TNF-α expression to attenuate inflammatory response in hippocampus. Moreover, anodal tDCS treatment could alleviate autophagy level. The study has demonstrated a possible therapeutic role of tDCS in the treatment of cognitive impairment in VD.

Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro

“…Furthermore, in an in vivo study performed in healthy mice, it has been observed that a prolonged exposure to high frequency electromagnetic field leads to an increase of autophagic proteins LC3-II and Beclin-1 and an accumulation of autolysosomes in neuronal cell bodies 23 . An attenuation of macroautophagy activation was also recently described in a rat model of vascular dementia 24 . Notably, all published studies investigated the effect of stimulation on macroautophagy, and no literature data are up to now available on CMA, although CMA dysfunctions has been recognized to play a crucial role in PD pathogenesis 12 .…”

Curcumin protects against cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressing neuroinflammation, apoptosis, and pyroptosis

“…Previous studies have reported that neuroin ammation plays a vital role in the pathology of VaD [14,[39][40][41] . Microglia are resident immune cells within the central nervous system and play an important role in the initiation and transmission of in ammatory responses.…”

Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?

“…Whilst studies investigating the inflammatory changes associated specifically with PSD in patients remain scarce, various experimental models of VaD have noted a link between neuroinflammation and neuronal damage following cerebral ischaemia. Specifically, a variety of experimental studies have observed an increase in pro-inflammatory cytokines in the hippocampus of VaD models [ 263 , 264 , 265 ]. Particularly, Zang et al demonstrated that rats with VaD (measured as severe neurological deficit following MCAo) had significantly higher levels of the inflammatory markers nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), TNF-α and IL-1β in the hippocampus compared to shams, and that this increase was associated with increased neuronal damage [ 266 ].…”