Increases in Microvascular Perfusion and Tissue Oxygenation via Vasodilatation After Anodal Transcranial Direct Current Stimulation in the Healthy and Traumatized Mouse Brain
Abstract:Traumatic brain injury (TBI), causing neurological deficit in 70% of survivors, still lacks a clinically proven effective therapy. Transcranial direct current stimulation (tDCS) has emerged as a promising electroceutical therapeutic intervention possibly suitable for TBI; however, due to limited animal studies the mechanisms and optimal parameters are unknown. Using a mouse model of TBI we evaluated the acute effects of the anodal tDCS on cerebral blood flow (CBF) and tissue oxygenation, and assessed its effic… Show more
“…Additionally, Bragina et al demonstrate an increased CBF (~26%; Fig. 1) in response to DC transcranial stimulation in mice, but only at a single dose of 0.1 mA for 15 min, assessing CBF through a sealed window over a craniotomy [41]. These authors also show an increased microvascular diameter in the cortex and reduced NADH response as well as an improvement in recovery of an open contusion head injury model with tDCS.…”
Section: Discussionmentioning
confidence: 92%
“…(For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.) maximal stimulation response [41]. Additionally, laser Doppler measurements are relative measures of CBF depending on location near vessels, hence the baseline values may vary considerably across the cortical surface.…”
Background: Transcranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses. Objective: We performed in vivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation. Methods: We performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation doseeresponse function between intracranial electric field and cerebral blood flow.Results: Stimulation at electric field amplitudes of 5e20 mV/mm at 10e20 Hz rapidly increased cerebral blood flow (within 100 ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimulation dose and peak blood flow increase. Neither afterdischarges nor spreading depression occurred from this level of stimulation. Conclusions: Extracranial stimulation amplitudes sufficient to evoke reliable blood flow changes require electric field strengths higher than what is tolerable in unanesthetized humans (<1 mV/mm), but less than electroconvulsive therapy levels (>40 mV/mm). However, anesthesia effects, spontaneous blood flow fluctuations, and sampling error may accentuate the apparent field strength needed for enhanced blood flow. The translation to a human doseeresponse function to augment cerebral blood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.
“…Additionally, Bragina et al demonstrate an increased CBF (~26%; Fig. 1) in response to DC transcranial stimulation in mice, but only at a single dose of 0.1 mA for 15 min, assessing CBF through a sealed window over a craniotomy [41]. These authors also show an increased microvascular diameter in the cortex and reduced NADH response as well as an improvement in recovery of an open contusion head injury model with tDCS.…”
Section: Discussionmentioning
confidence: 92%
“…(For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.) maximal stimulation response [41]. Additionally, laser Doppler measurements are relative measures of CBF depending on location near vessels, hence the baseline values may vary considerably across the cortical surface.…”
Background: Transcranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses. Objective: We performed in vivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation. Methods: We performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation doseeresponse function between intracranial electric field and cerebral blood flow.Results: Stimulation at electric field amplitudes of 5e20 mV/mm at 10e20 Hz rapidly increased cerebral blood flow (within 100 ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimulation dose and peak blood flow increase. Neither afterdischarges nor spreading depression occurred from this level of stimulation. Conclusions: Extracranial stimulation amplitudes sufficient to evoke reliable blood flow changes require electric field strengths higher than what is tolerable in unanesthetized humans (<1 mV/mm), but less than electroconvulsive therapy levels (>40 mV/mm). However, anesthesia effects, spontaneous blood flow fluctuations, and sampling error may accentuate the apparent field strength needed for enhanced blood flow. The translation to a human doseeresponse function to augment cerebral blood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.
“…The application of tDCS in neurorehabilitation is not surprising, since it can be used to increase or decrease brain function and learning [47–50], and it is considered safe and well-tolerated [51, 52]. Evidence from DCS clinical trials is further supported by animal models of injury recovery [39, 53–57]. Fig.…”
Section: Physiological Basis and Functional Connectivity Of Tdcs In Mmentioning
Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.
“…However, earlier stimulation only improved spatial memory [31]. In a later phase of TBI, it was possible to observe motor recovery as well as spatial memory improvement following repeated anodal tDCS [48]. A growing number of studies has been reporting promising effects of neurostimulation in models of addictive disorders, by reducing craving and maladaptive pervasive learning [49].…”
Brain stimulation techniques, including transcranial direct current stimulation (tDCS), were identified as promising therapeutic tools to modulate synaptic plasticity abnormalities and minimize memory and learning deficits in many neuropsychiatric diseases. Here, we revised the effect of tDCS on the modulation of neuroplasticity and cognition in several animal disease models of brain diseases affecting plasticity and cognition. Studies included in this review were searched following the terms (“transcranial direct current stimulation”) AND (mice OR mouse OR animal) and according to the PRISMA statement requirements. Overall, the studies collected suggest that tDCS was able to modulate brain plasticity due to synaptic modifications within the stimulated area. Changes in plasticity-related mechanisms were achieved through induction of long-term potentiation (LTP) and upregulation of neuroplasticity-related proteins, such as c-fos, brain-derived neurotrophic factor (BDNF), or N-methyl-D-aspartate receptors (NMDARs). Taken into account all revised studies, tDCS is a safe, easy, and noninvasive brain stimulation technique, therapeutically reliable, and with promising potential to promote cognitive enhancement and neuroplasticity. Since the use of tDCS has increased as a novel therapeutic approach in humans, animal studies are important to better understand its mechanisms as well as to help improve the stimulation protocols and their potential role in different neuropathologies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
