Low-intensity pulsed ultrasound improves behavioral functions and alleviates neuroinflammation in a rat model of Parkinson’s disease

Abstract BackgroundParkinson’s disease (PD) is characterized by a reduction of dopamine level in the substantia nigra pars compacta (SNpc) and striatum of the brain. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated recently as a non-invasive neuromodulation tool in a number of fields. LIPUS has also been reported to improve behavioral functions in PD animal models; however, the effect of LIPUS stimulation on the neurotrophic factors and neuroinflammation has not yet been addressed.MethodsPD rat model was built by injection of 6-hydroxydopamine (6-OHDA) in two sites in the right striatum. The levels of neurotrophic factors and lipocalin-2 (LCN2)-induced neuroinflammation were quantified using a western blot. Rotational test and cylinder test were conducted biweekly for eight weeks. The safety of LIPUS was assessed using Hematoxylin and Esosin (H&E) staining and Nissl staining.ResultsWhen the 6-OHDA+LIPUS and 6-OHDA groups were compared, the locomotor function of the 6-OHDA+LIPUS rats was significantly improved. After LIPUS stimulation, the number of neurons was remarkably increased in the striatum and SNpc of lesioned rats. Unilateral LIPUS stimulation did not increase brain-derived neurotrophic factor (BDNF) in the striatum and SNpc of lesioned rats. In contrast, unilateral LIPUS stimulation increased glial cell line-derived neurotrophic factor (GDNF) protein 1.98-fold unilaterally in the SNpc. Additionally, LCN2-induced neuroinflammation can be attenuated following LIPUS stimulation.ConclusionsOur data indicated that LIPUS stimulation increased GDNF and dopaminergic (DA) neuron density in the 6-OHDA-induced rat model of PD. Moreover, this technology attenuated proinflammatory mediators and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of brain tissue injury. These results show that LIPUS stimulation may be a potential therapeutic tool against PD via enhancement of GDNF level and inhibition of inflammatory responses in the SNpc of the brain.

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Low-Intensity Pulsed Ultrasound Prompts Both Functional and Histologic Improvements While Upregulating the Brain-Derived Neurotrophic Factor Expression after Sciatic Crush Injury in Rats

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2021.02.009 ◽

2021 ◽

Vol 47 (6) ◽

pp. 1586-1595

Author(s):

Tianshu Wang ◽

Akira Ito ◽

Shixuan Xu ◽

Hideki Kawai ◽

Hiroshi Kuroki ◽

...

Keyword(s):

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Crush Injury ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Factor Expression ◽

The Brain

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Low Intensity Pulsed Ultrasound Prevents Recurrent Ischemic Stroke in a Cerebral Ischemia/Reperfusion Injury Mouse Model via Brain-derived Neurotrophic Factor Induction

International Journal of Molecular Sciences ◽

10.3390/ijms20205169 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5169 ◽

Cited By ~ 2

Author(s):

Cheng-Tien Wu ◽

Ting-Hua Yang ◽

Man-Chih Chen ◽

Yao-Pang Chung ◽

Siao-Syun Guan ◽

...

Keyword(s):

Mouse Model ◽

Neurotrophic Factor ◽

Recurrent Stroke ◽

Brain Derived Neurotrophic Factor ◽

Stroke Recurrence ◽

Therapeutic Effects ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Therapeutic Benefits

The incidence of stroke recurrence is still higher despite the advanced progression of therapeutic treatment and medical technology. Low intensity pulsed ultrasound (LIPUS) has been demonstrated to possess therapeutic effects on neuronal diseases and stroke via brain-derived neurotrophic factor (BDNF) induction. In this study, we hypothesized that LIPUS treatment possessed therapeutic benefits for the improvement of stroke recurrence. Adult male C57BL/6J mice were subjected to a middle cerebral artery occlusion (MCAO) surgery and then followed to secondary MCAO surgery as a stroke recurrence occurred after nine days from the first MCAO. LIPUS was administered continuously for nine days before secondary MCAO. LIPUS treatment not only decreased the mortality but also significantly moderated neuronal function injury including neurological score, motor activity, and brain pathological score in the recurrent stroke mice. Furthermore, the administration of LIPUS attenuated the apoptotic neuronal cells and increased Bax/Bcl-2 protein expression ratio and accelerated the expression of BDNF in the brain of the recurrent stroke mice. Taken together, these results demonstrate for the first time that LIPUS treatment arouses the expression of BDNF and possesses a therapeutic benefit for the improvement of stroke recurrence in a mouse model. The neuroprotective potential of LIPUS may provide a useful strategy for the prevention of a recurrent stroke.

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