Sung Chen-Yu, Chiang Pai-Kai, Tsai Che-Wen, Yang Feng-Yi
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan.
Cereb Cortex. 2021 Nov 23;32(1):176-185. doi: 10.1093/cercor/bhab201.
Low-intensity pulsed ultrasound (LIPUS) has also been reported to improve behavioral functions in Parkinson's disease (PD) animal models; however, the effect of LIPUS stimulation on the neurotrophic factors and neuroinflammation has not yet been addressed. PD rat model was built by injection of 6-hydroxydopamine (6-OHDA) in 2 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 8 weeks. When 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 tyrosine hydroxylase staining density was significantly increased in the striatum and substantia nigra pars compacta (SNpc) of lesioned rats. Unilateral LIPUS stimulation did not increase brain-derived neurotrophic factor 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. Our data indicated 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.
据报道,低强度脉冲超声(LIPUS)可改善帕金森病(PD)动物模型的行为功能;然而,LIPUS刺激对神经营养因子和神经炎症的影响尚未得到研究。通过在右侧纹状体的两个部位注射6-羟基多巴胺(6-OHDA)建立PD大鼠模型。使用蛋白质印迹法定量神经营养因子和脂钙蛋白-2(LCN2)诱导的神经炎症水平。每两周进行一次旋转试验和圆筒试验,持续8周。比较6-OHDA+LIPUS组和6-OHDA组时,6-OHDA+LIPUS大鼠的运动功能明显改善。LIPUS刺激后,损伤大鼠纹状体和黑质致密部(SNpc)的酪氨酸羟化酶染色密度显著增加。单侧LIPUS刺激并未增加损伤大鼠纹状体和SNpc中的脑源性神经营养因子。相反,单侧LIPUS刺激使SNpc中的胶质细胞源性神经营养因子(GDNF)蛋白单侧增加了1.98倍。此外,LIPUS刺激后可减轻LCN2诱导的神经炎症。我们的数据表明,LIPUS刺激可能是一种潜在的治疗PD的工具,通过提高GDNF水平和抑制脑SNpc中的炎症反应来实现。