Stimulated by Yao et al 2023.[1]
PSD – post-stroke dysphagia
key to acronyms
IF – impact factor
EA – electroacupuncture
aka – also known as
ROS – reactive oxygen species
M1 – primary motor cortex
PBN – parabrachial nucleus
NTS – nucleus tractus solitarius
I am pretty selective about choosing laboratory studies to highlight on the blog. I do not have direct experience of performing laboratory research, so I must rely on indirect metrics of quality. This paper was published in Nature Communications (IF 17.69) and is a typical multi-layered piece of work involving many different experiments to complete a mechanistic picture.
I was also attracted to it because in tests a simple EA protocol at a favourite location (CV23). The subject matter (PSD) is an important functional sequela of stroke and although acupuncture is not used to any significant degree for this indication in the West, this research provides robust mechanistic data supporting the potential efficacy of EA. In addition to this, some of the methods used in the experiments are entirely new to me, despite some of them being first described when I was at medical school around 40 years ago.[2,3]
I am referring to the use of stereotactic application of laser to activate a chemical (Rose Bengal) and create a very limited area of cortical ischaemia to mimic thrombotic stroke. When irradiated with photons at a wavelength of 560nm (green laser), the anionic xanthene dye, Rose Bengal, produces singlet oxygen (1O2) aka dioxidene, which is one form of ROS.
It is quite astonishing what can now be achieved with different classes of, what are referred to as, optical probes and reporters.[4] These are proteins that can sit in neural membranes and emit photons when there are changes in voltage, calcium flux, receptor activity, or synaptic release, and other protein channels and transporters can be activated or inhibited by targeting them with photons of a particular wavelength, thus precisely manipulating activity in target neurons as well as precisely monitoring such activity.
Back to the Rose Bengal creating ROS on irradiation with a green laser… when this is done in a small artery in a specific part of the cerebral cortex it results in thrombosis of the artery and ischaemia in a very targeted region of the brain. In this case the researchers targeted lamina 5 neurones in the primary motor cortex (M1) responsible for control of the omohyoid muscle. The omohyoid muscle attaches the hyoid bone to the inside of the mandible and elevates the hyoid during swallowing. It is also one of the targets of needling and EA at CV23.
I have discussed my appreciation of CV23 in a previous blog: Acupuncture for PSA.
The main result was that EA applied at 2Hz and 1mA for 15 minutes to CV23 could almost completely reverse the dysphagia created by a relatively discrete cortical infarct in M1. The optimal timing of EA was 24 hours after induction of the stroke model.
Dysphagia was assessed by the water consumption test over a 4-minute period following 24 hours without water.
You might think that what I have already described in terms of creating the stroke dysphagia model sounds rather complex, but there is a lot more complex experimentation in this paper. They performed a number of experiments with viral tracers related to polio, rabies, and adenoviruses in order to determine the neural connections and the precise region of the M1 cortex involved in swallowing. A blue laser (473nm) was used to stimulate these M1 excitatory neurones in vivo. The neurons had been infected with a modified adenovirus coding for a light sensitive channel (AAV2-CaMKIIα-ChR2-mCherry). EMG recording from omohyoid together with a pharyngeal pressure transducer were used to confirm the motor control link to swallowing.
Further experiments revealed neural circuits in the PBN and NTS were involved and importantly, the effect of EA at CV23 was dependent on not only these circuits, but on the increased neuronal activity in lamina 5 of the M1 cortex contralateral to the ischaemia.
The authors conclude:
These findings not only elucidate a critical pathway for understanding how the motor cortex controls the swallowing process, but also suggest a potential valuable treatment strategy for swallowing-related disorders.
References
1 Yao L, Ye Q, Liu Y, et al. Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei. Nat Commun 2023;14:810. doi:10.1038/s41467-023-36448-6
2 Watson BD, Dietrich WD, Busto R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 1985;17:497–504. doi:10.1002/ana.410170513
3 Talley Watts L, Zheng W, Garling RJ, et al. Rose Bengal Photothrombosis by Confocal Optical Imaging In Vivo: A Model of Single Vessel Stroke. J Vis Exp JoVE 2015;:e52794. doi:10.3791/52794
4 Scanziani M, Häusser M. Electrophysiology in the age of light. Nature 2009;461:930–9. doi:10.1038/nature08540
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