The ability of afobazole, a selective anxiolytic to prevent the brain local ischemia-induced anxiety has been studied in experiments on rats. It is established that middle cerebral artery occlusion (MCAO) is accompanied by the development of anxiety, the degree of which increases with the duration of occlusion. Afobazole in a doze of 1 mg/kg administrated during 6 days after MCAO prevents the development of anxiety. The effect is manifested by positive changes in the parameters describing the behavior of animals in elevated plus maze test. No tolerance to the drug is developed during continuous afobazole injection within 12 days after MCAO. The experimental data indicate that the well-known anxiolytic action of afobazole is also well pronounced under the conditions of a local cerebrtal ischemia.
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Preclinical Alzheimer's prevention trials require a multi-year commitment from diverse, cognitively unimpaired individuals willing to receive biomarker results of confirmed Alzheimer's pathology and possible ApoE4 status. Participants learn new terms such as ARIA, edema and microhemorrhage and undergo numerous MRI scans for safety monitoring. They take quarterly composite Alzheimer's assessments that are anxiety-provoking and highlight weaknesses which may have been unrecognized in daily life.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a complex disease that is often accompanied by a range of comorbidities, such as cardiovascular disease, diabetes, and depression. These comorbidities can impact the progression of AD and can complicate treatment strategies. Targeting comorbidities in Alzheimer's disease and developing combination therapies are emerging areas of research.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Background: Participant dropout from study treatment in a clinical trial can leave a trial underpowered, produce bias in statistical analysis, and limit interpretability of study results. Retaining participants in clinical trials for the full study duration is therefore as important as participant recruitment. This analysis aims to identify the baseline characteristics of participants who discontinued during the blinded phase of one of the first and largest preclinical AD trial completed to date, the Anti-Amyloid treatment in Asymptomatic AD (A4) Study.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA.
Background: Apolipoprotein E4 (apoE4) has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Our lab has demonstrated that chronic administration of Aβ12-28P, a synthetic peptide that blocks apoE4/Aβ binding, in middle-aged transgenic AD mice significantly ameliorates pathology progression, resulting in reduced Aβ plaques deposition and cerebral amyloid angiopathy (CAA) along with improved memory and cognition. However, whether blocking apoE4/Aβ interaction by Aβ12-28P also has an ameliorating effect on the neuronal and cognitive function of old AD mice where Aβ pathology has been extensively developed remains unknown.
View Article and Find Full Text PDFBackground: Focused Ultrasound-induced Blood-Brain Barrier Opening (FUS-BBBO) has demonstrated preventative and therapeutic efficacy for improving cognitive and pathological decline in Alzheimer's Disease (AD). Previous work has demonstrated highly specific binding of a novel Re complex (Re-1) complex to amyloid-β (Aβ) in vitro, subsequently inhibiting fibril formation and reducing Aβ-induced cytotoxicity in neuronal cell cultures. The aim of this preliminary study is to evaluate the efficacy of early intervention combining FUS-BBBO and Re-1 for anxiety amelioration and memory improvement in a triple transgenic (3xTg)-AD mouse model.
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