Donepezil Protects Against Doxorubicin-Induced Chemobrain in Rats via Attenuation of Inflammation and Oxidative Stress Without Interfering With Doxorubicin Efficacy

Although doxorubicin (Dox) is an effective chemotherapy medication used extensively in the treatment of breast cancer, it frequently causes debilitating neurological deficits known as chemobrain. Donepezil (DPZ), an acetylcholinesterase inhibitor, provides therapeutic benefits in various neuropathological conditions. However, comprehensive mechanistic insights regarding the neuroprotection of DPZ on cognition and brain pathologies in a Dox-induced chemobrain model remain obscure. Here, we demonstrated that Dox-treated rats manifested conspicuous cognitive deficits and developed chemobrain pathologies as indicated by brain inflammatory and oxidative insults, glial activation, defective mitochondrial homeostasis, increased potential lesions associated with Alzheimer’s disease, disrupted neurogenesis, loss of dendritic spines, and ultimately neuronal death through both apoptosis and necroptosis. Intervention with DPZ co-treatment completely restored cognitive function by attenuating these pathological conditions induced by DOX. We also confirmed that DPZ treatment does not affect the anti-cancer efficacy of Dox in breast cancer cells. Together, our findings suggest that DPZ treatment confers potential neuroprotection against Dox-induced chemobrain.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01092-9.     

Chronic treatment with prebiotics,probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats

European Journal of Nutrition - In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics,...     

An apoptosis inhibitor suppresses microglial and astrocytic activation after cardiac ischemia/reperfusion injury

Inflammation Research - Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that...     

BAK椎间融合器治疗轻度腰椎峡部型滑脱症

自1997年4月～1998年4月间,以多孔螺纹状椎间融合器(BAK)行后路腰椎椎体融合术(PLIF)治疗8例轻度L_5/S_1峡部型滑脱症病人。患者主要症状为反复发作的下腰痛,伴有一侧(5例)或双侧(3例)的下肢疼痛。术前侧位X线片显示腰5椎体轻度向前滑脱(15％～30％滑移程度),且该椎间隙高度较邻近之正常间隙降低30％以上;斜位片示峡部裂隙6例(其中1例为单侧)、峡部细长2例。双侧症状者行后前向双枚BAK椎间融合器PLIF。术后平均随访12月,皆达到临床融合。所有患者均无融合器的移位,患者主观满意率100％。作者认为,BAK椎间融合器植入行后路腰椎椎体间融合术,能充分完成后路减压、保证可靠的融合,且无需应用附加内固定,不失为一种比较理想的治疗轻度腰椎峡部型滑脱手术方法。     

Altered gut microbiota ameliorates bone pathology in the mandible of obese–insulin-resistant rats

The chronic consumption of a high-fat diet (HFD) induces obese–insulin resistance and impairs jawbone health via gut dysbiosis-stimulated inflammator     

A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats

Metabolic Brain Disease - Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a...     

The possible factors affecting microglial activation in cases of obesity with cognitive dysfunction

Obesity has reached epidemic proportions in many countries around the world. Several studies have reported that obesity can lead to the development of cognitive decline. There is increasing evidence to demonstrate that microglia play a crucial role in cognitive decline in cases of obesity, Alzheimer’s disease and also in the aging process. Although there have been several studies into microglia over the past decades, the mechanistic link between microglia and cognitive decline in obese models is still not fully understood. In this review, the current available evidence from both in vitro and in vivo investigations regarding the association between the alteration in microglial activity in different obese models with respect to cognition are included. The metabolite profiles from obesity, adiposity, dietary and hormone affected microglial activation and its function in the brain are comprehensively summarized. In addition, the possible roles of microglial activation in relation to cognitive dysfunction are also presented and discussed. To ensure a balanced perspective controversial reports regarding these issues are included and discussed.