Developing Treatment Options for Vascular Dementia --- Taiwan Research Team Stimulated Mouse Brain for Neurogenesis by Ultrasound, Published in the Journal eLife

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Doublecortin staining in mouse dentate gyrus was increased significantly after repeated ultrasound stimulation.

The Ministry of Science and Technology (MOST) is dedicated to the scientific and technological developmemt, not only to pursue academic excellence, but also hope to translate the research output to the improvement of human well-being.  With the support of “Taiwan Brain Technology Development and International Raising Program” promoted by MOST, an interdisciplinary team, consisting of Prof. Jaw-Lin Wang of National Taiwan University, Prof. Chih-Cheng Chen of Academia Sinica, Dr. Wen-Shiang Chen and Dr. Dar-Ming Lai of NTU Hospital, explored the possibility to use low intensity ultrasound for treatments of vascular dementia. Their findings have been published in the journal eLife [1]. The physicians in the team are actively pursuing translating research results for clinical applications..

Vascular dementia can be caused by strokes and often leads to cognitive impairment and behavior disorder, causing a tremendous burden to families and society in large. Stroke is also one of the main diseases for mortality and among the top 4 causes for death in Taiwan. More than twelve thousand people dies from stroke each year in Taiwan. While the progress of medical care has reduced the death rate by stroke, vascular dementia induced by stroke nevertheless leads to costly medical bills for patients in their long-term care.

The research team led by Professor Jaw-Lin Wang explored possible treatment options for vascular dementia with low intensity transcranial ultrasound. The team developed a micropipette guided ultrasound device (Figure 1, upper panel) that can radiate ultrasound from a glass pipette tip much smaller than cells to modulate neurons. Under the supervision of Prof. Chih-Cheng Chen of Academia Signai, the team activated intracellular calcium in neurons with this device and correlated the results with findings in tissues and animal studies. They showed ultrasound can modulate intracellular calcium in neurons through the ion channel ASIC1a (Figure 1, lower panel) and affect the downstream signal pathways.  

To explore possible clinical application of the identified biological mechanism, the team developed a protocol to stimulate mouse brain and found Doublecortin staining, i.e. a neurogenesis bio marker, was significantly increased by ultrasound treatments (Figure 2). This suggests possible neurogenesis enhanced by ultrasound stimulation. Neurogenesis can be leveraged as a basis to repair damaged neurons for vascular dementia treatments. In summary, this work established a fundamental molecular mechanism for ultrasound neuromodulation in the brain and provided the basis for a possible therapeutic approach for ultrasound based vascular dementia treatments.

[1] ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain, Jormay Lin, …, Chih-Cheng Chen, Jaw-Lin Wang, eLife 2021; 10: e61660. (https://elifesciences.org/articles/61660)

Figure 1: Micropipette guided ultrasound device (upper) and intracellular calcium induced by micropipette ultrasound (lower).

Figure 1: Micropipette guided ultrasound device (upper) and intracellular calcium induced by micropipette ultrasound (lower).

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