Progress in Neurobiology最新文献

Traumatic brain injuries (TBI) significantly increase the risk of both ischemic and hemorrhagic strokes, with effects persisting for years after the initial injury. The mechanisms underlying this increased stroke risk are complex, multifactorial, and incompletely understood but likely include chronic cerebrovascular dysfunction, blood-brain barrier disruption, and inflammatory responses. Epidemiological studies consistently show that TBI is an independent risk factor for stroke, with more severe injuries associated with greater risk, especially for hemorrhagic strokes. Traditional risk factors for stroke, such as hypertension, poor diet, and sedentary lifestyle, further elevate the risk in TBI survivors. Modifiable lifestyle factors, such as improving sleep, increasing physical activity, and adopting heart-healthy diets, offer potential intervention points to mitigate stroke risk. Pharmacological considerations, including the use of antidepressants, anticoagulants, and statins, also influence stroke risk, particularly with regard to hemorrhagic complications. This review explores the pathophysiological mechanisms linking TBI and stroke, emphasizing the need for future research to identify specific biomarkers and imaging techniques to predict stroke vulnerability in TBI patients. Addressing the gaps in understanding, particularly regarding small vessel pathology will be essential to developing targeted therapies for reducing stroke incidence in TBI survivors.

Introduction: The interaction of amyloid and tau in neurodegenerative diseases is a central feature of AD pathophysiology. While experimental studies point to various interaction mechanisms, their causal direction and mode (local, remote or network-mediated) remain unknown in human subjects. The aim of this study was to compare mathematical reaction-diffusion models encoding distinct cross-species couplings to identify which interactions were key to model success.

Methods: We tested competing mathematical models of network spread, aggregation, and amyloid-tau interactions on publicly available data from ADNI.

Results: Although network spread models captured the spatiotemporal evolution of tau and amyloid in human subjects, the model including a one-way amyloid-to-tau aggregation interaction performed best.

Discussion: This mathematical exposition of the "pas de deux" of co-evolving proteins provides quantitative, whole-brain support to the concept of amyloid-facilitated-tauopathy rather than the classic amyloid-cascade or pure-tau hypotheses, and helps explain certain known but poorly understood aspects of AD.

Sleep disorders can increase amyloid beta (Aβ) burden in the brain and are linked to Alzheimer's disease (AD) risk. The precise mechanism by which sleep disturbances elevate Aβ levels is unclear. Our previous study has demonstrated that knocking down encoding gene Grin2a of astrocytic N-methyl-D-aspartate (NMDA) receptors GluN2A subunit could aggravate sleep deprivation (SD)-induced elevation of Aβ, indicating a protective role of astrocytic GluN2A in SD; but the underlying mechanism needs to be further elucidated. In our present study, using rat models of SD combined with specific astrocytic Grin2a knockdown or overexpression in the hippocampus, and a cell model of primary cultured hippocampal astrocytes, we reveal a novel mechanism that astrocytic GluN2A alleviates SD-induced increases in Aβ. We demonstrated that astrocytic GluN2A mainly affected Aβ degradation and clearance through regulating degradation enzyme neprilysin and Aquaporin-4 (AQP4), via the calcineurin/NFAT pathway. Our study provides supportive evidence for the novel role and mechanism of astrocytic GluN2A in Aβ elimination, which would contribute to the discovery of new therapeutic strategies for Aβ-related diseases such as AD.