Low-Intensity Pulsed Ultrasound Attenuates LPS-Induced Neuroinflammation and Memory Impairment by Modulation of TLR4/NF-κB Signaling and CREB/BDNF Expression

The purpose of this study was to investigate the restorative role of low-intensity pulsed ultrasound (LIPUS) against lipopolysaccharide (LPS)-induced neuroinflammation and memory impairments in a simulation of Alzheimer's disease. Mice subjected to LPS administration (250 mu g/kg, i.p.) were treated with LIPUS daily for 7 days. The levels of brain-derived neurotrophic factor (BDNF) and inflammatory markers were estimated in brain tissue using western blot. After LIPUS treatment, the neuroprotective effects of LIPUS in mice were assessed by behavioral tests. LPS plus LIPUS-treated mice exhibited a significant increase in the average time spent in the target quadrant compared to the LPS-treated group. Compared with the LPS-treated group, LPS plus LIPUS-treated mice revealed a preference for the novel object. LIPUS treatment significantly attenuated LPS-induced increases in the expression of amyloid-beta (A beta) and amyloid precursor protein (APP) in the hippocampus region of LPS-treated mice. Furthermore, LIPUS significantly reduced the protein levels of TNF-alpha, IL-1 beta, and IL-6 in the mice brain induced by LPS. LIPUS treatment induces neuroprotection by inhibiting the LPS-induced activation of TLR4/NF-kappa B inflammatory signaling and by enhancing the associated CREB/BDNF expression in LPS-treated mice. Our data showed that LIPUS attenuated LPS-induced memory impairment as well as amyloidogenesis via the suppression of neuroinflammatory activity and BDNF decline.