β2-Microglobulin exacerbates neuroinflammation,brain damage,and cognitive impairment after stroke in rats

β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Alzheimer Disease and Music-Therapy: An Interesting Therapeutic Challenge and Proposal

Aim: The aim of this study is to highlight the effectiveness of music therapy in Alzheimer’s Disease (AD) and their caregivers. Methods: The biennial 2019 to 2020, 32 patients, with AD (ICD-10), were examined, by a research group composed by a Neurologist, a GP and a Music-psychotherapist. All patients were under pharmaceutical care. The patients’ medical record and musical profile was assessed. The answers were provided by the patients themselves or by their tutors. Then, personal or family sessions were organized with the participation of musical instruments. The patients staging and evaluation were made through MMSE. The test was repeated every six months under the Neurologist’s supervision. Finally, 31 totally patients succeeded to complete our intervention and to be estimated. Results: The duration of follow-up of the patients was 30 months. At the beginning and end of the sessions we obtained the following data: In a total of 32 patients with AD, initially 3 patients (9.37%) had Mild AD, 19 patients (59.37%) had Moderate AD, 10 patients (31.25%) severe AD, based on the MMSE evaluation. After 30 months, 11 patients had Mild AD (35.48%), number resulting from the music benefit of cognitive function in patients with moderate AD. 15 patients with Moderate AD (48.38%) were observed, out of the initial 19 (59.37%) patients with Moderate AD, a number attributed to the sum of patients who improved from severe AD and those who were transferred, benefiting from treatment, from Moderate AD disease to Mild AD. Finally 5 patients with severe AD disease were evaluated (16.12%), while before the treatment we had 10 patients (31.25%) with severe AD. Conclusions: Music therapy is a tool to increase the life quality of the participants. The results expected in the treatment of AD are obtained by means of good collaboration among the research team.

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

Alzheimer's disease(AD)is a prevalent neurodegenerative disorder characterized by gradual deterioration of cognitive functions,for which an effective treatment is currently unavailable.Repetitive transcranial magnetic stimulation(rTMS),a well-established noninvasive brain stimulation method,is utilized in clinical settings to address various neuropsychiatric conditions,such as depression,neuropathic pain,and poststroke dys-function.Increasing evidence suggests that rTMs may enhance cognitive abilities in individuals with AD.However,its optimal therapeutic protocols and precise mechanisms are currently unknown,impeding its clinical implementation.In the present review,we aimed to summarize and discuss the efficacy-related parameters in rTMs treatment,encompassing stimulus frequency,stimulus pattern,stimulus intensity,and the configuration of the stimulus coil.Furthermore,we reviewed promising rTMS therapeutic protocols involving various combinations of these factors,that were examined in clinical studies.Based on our analysis,we propose that a multisite high-frequency rTMS(HF-rTMS)regimen has value in AD therapy,and that promising single-site protocols,such as HF-rTMS,applied over the left dorsolateral prefrontal cortex,precuneus,or cerebellum are required to be validated in larger clinical studies.Lastly,we provide a comprehensive review of the potential mechanisms underlying the neuroprotective effects of rTMS on cognition in AD in terms of brain network modulation as well as cellular and molecular reactions.In conclusion,the interaction of diverse mechanisms may be responsible for the total therapeutic effect of rTMS on AD.This review provides theoretical and practical evidence for the future clinical application and scientific research of rTMS in AD.

Coassembly of Macrocyclic Amphiphiles for Anti-β-Amyloid Therapy of Alzheimer’s Disease

Based on the amyloid hypothesis,anti-β-amyloid(Aβ)therapy has dominated clinical trials for the prevention and treatment of Alzheimer’s disease(AD)in recent years.A key element of this strategy is the interaction between therapeutic agents and Aβ.However,the design and development of artificial receptors that may render selective and strong recognition toward Aβremains a huge challenge because of the complexity and size of peptide guests and their flexible conformation.