Transcranial Low-Intensity Pulsed Ultrasound Modulates Structural and Functional Synaptic Plasticity in Rat Hippocampus

Huang, Xiaowei; Lin, Zhengrong; Wang, Kaiyue; Liu, Xiufang; Zhou, Wei; Meng, Long; Huang, Jiqing; Yuan, Kun; Niu, Lili; Zheng, Hairong

doi:10.1109/tuffc.2019.2903896

Cited by 33 publications

(27 citation statements)

References 67 publications

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“…16,55 Previous studies also suggest that mechanical ultrasound effects can modulate the firing patterns of primary cultures of hippocampal cells, and increase excitatory postsynaptic current (EPSCs) frequency in rat hippocampal pyramidal neurons. 16,56 Previous studies have demonstrated that LIPUS produces excitatory or inhibitory neuromodulation largely depending on its parameters, 57 but there is still no consensus on what parameters of LIPUS stimulation can produce excitatory or inhibitory effects. Here, we demonstrated that LIPUS stimulation with the parameters chosen in our study can activate vmPFC neurons in vivo.…”

Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound ameliorates depression‐like behaviors in a rat model of chronic unpredictable stress

et al. 2020

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Introduction There is an unmet need for better nonpharmaceutical treatments for depression. Low‐intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. Objective The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. Methods Chronic unpredictable stress (CUS) was used to generate rats with depression‐like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression‐like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin‐eosin and Nissl staining. Results Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal‐regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. Conclusions Chronic LIPUS stimulation can effectively and safely improve depression‐like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression.

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Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound ameliorates depression‐like behaviors in a rat model of chronic unpredictable stress

et al. 2020

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“…2 ). Also, LIFUS (360-760 mW/cm 2 ) activates the cerebral cortex as measured by c-Fos expression [ 91 , 92 ] (Fig. 2 ) and electroencephalography [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence

Pérez-Neri

González-Aguilar

Sandoval

et al. 2021

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Background: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies - as focused ultrasound (FUS) neuromodulation - has revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. Objective: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. Methods: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. Discussion: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain managing as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also effective useful in lowering non-neuropathic pain in several disorders. Conclusion: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

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“…Previous studies indicated that a 0.75°C rise in temperature induced by ultrasound stimulation has little impact on the biological effects in hippocampus tissue [57]. Our previous studies have shown that the mechanical effect, other than the thermal effect, played an important role in the neuromodulation for Caenorhabditis elegans [58], ex vivo brain slices [59, 60], and rodents [61, 62]. Lastly, according to HE and Nissl staining assessments, there was no tissue damage along the acoustic beam path after 7 days of ultrasound stimulation (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Ultrasound Deep Brain Stimulation for the Treatment of Parkinson’s Disease Model Mouse

et al. 2019

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Modulating basal ganglia circuitry is of great significance in the improvement of motor function in Parkinson’s disease (PD). Here, for the first time, we demonstrate that noninvasive ultrasound deep brain stimulation (UDBS) of the subthalamic nucleus (STN) or the globus pallidus (GP) improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunohistochemical c-Fos protein expression confirms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group (both p < 0.05). Furthermore, STN-UDBS or GP-UDBS significantly increases the latency to fall in the rotarod test on day 9 (p < 0.05) and decreases the time spent climbing down a vertical rod in the pole test on day 12 (p < 0.05). Moreover, our results reveal that STN-UDBS or GP-UDBS protects the dopamine (DA) neurons from MPTP neurotoxicity by downregulating Bax (p < 0.001), upregulating Bcl-2 (p < 0.01), blocking cytochrome c (Cyt C) release from mitochondria (p < 0.05), and reducing cleaved-caspase 3 activity (p < 0.01) in the ipsilateral substantia nigra (SN). Additionally, the safety of ultrasound stimulation is characterized by hematoxylin and eosin (HE) and Nissl staining; no hemorrhage or tissue damage is detected. These data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice, potentially serving as a noninvasive strategy for the clinical treatment of PD.

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Transcranial Low-Intensity Pulsed Ultrasound Modulates Structural and Functional Synaptic Plasticity in Rat Hippocampus

Cited by 33 publications

References 67 publications

Low‐intensity pulsed ultrasound ameliorates depression‐like behaviors in a rat model of chronic unpredictable stress

Low‐intensity pulsed ultrasound ameliorates depression‐like behaviors in a rat model of chronic unpredictable stress

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence

Noninvasive Ultrasound Deep Brain Stimulation for the Treatment of Parkinson’s Disease Model Mouse

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