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

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.