| First Author | Bobola MS | Year | 2020 |
| Journal | Brain Stimul | Volume | 13 |
| Issue | 4 | Pages | 1014-1023 |
| PubMed ID | 32388044 | Mgi Jnum | J:348198 |
| Mgi Id | MGI:6728323 | Doi | 10.1016/j.brs.2020.03.016 |
| Citation | Bobola MS, et al. (2020) Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Abeta load chronically, as demonstrated in vivo. Brain Stimul 13(4):1014-1023 |
| abstractText | OBJECTIVE: Iaccarino et al. (2016) [1] exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer's Disease (AD) mouse models, generating action potentials at 40 Hz, activating approximately 54% of microglia to colocalize with Abeta plaque, acutely, and clearing approximately 50% of Abeta plaque after seven days, but only in the visual cortex. HYPOTHESIS: Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) [1] but throughout its area of application. METHODS: We exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 mus-long pulses, spatial peak pulse average value of 190 W/cm(2)). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days. RESULTS: Acute application of tFUS activated more microglia that colocalized with Abeta plaque relative to sham ultrasound (36.0 +/- 4.6% versus 14.2 +/- 2.6% [mean +/- standard error], z = 2.45, p < 0.014) and relative to the contralateral hemisphere of treated brain (36.0 +/- 4.6% versus 14.3 +/- 4.0%, z = 2.61, p < 0.009). Chronic application over five days reduced their Abeta plaque burden by nearly half relative to paired sham animals (47.4 +/- 5.8%, z = - 2.79, p < 0.005). CONCLUSION: Our results compare to those of Iaccarino et al. (2016) [1] but throughout the area of ultrasound-exposed brain. Our results also compare to those achieved by medications that target Abeta, but over a substantially shorter period of time. The proximity of our ultrasound protocol to those shown safe for non-human primates and humans may motivate its rapid translation to human studies. |
