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Charged particle beams induce various biological effects by creating high‐density ionization through the deposition of energy along the beam's trajectory. Charged particle beams composed of neon ions (20Ne10+) hold great potential for biomedical applications, but their physiological effects on living organs remain uncertain. In this study, we demonstrate that neon‐ion beams expedite the process of reoxygenation in tumor models. We simulated mouse SCCVII syngeneic tumors and exposed them to either X‐ray or neon‐ion beams. Through an in vivo radiobiological assay, we observed a reduction in the hypoxic fraction in tumors irradiated with 8.2 Gy of neon‐ion beams 30 h after irradiation compared to 6 h post‐irradiation. Conversely, no significant changes in hypoxia were observed in tumors irradiated with 8.2 Gy of X‐rays. To directly quantify hypoxia in the irradiated living tumors, we utilized dynamic contrast‐enhanced magnetic resonance imaging (MRI) and diffusion‐weighted imaging. These combined MRI techniques revealed that the non‐hypoxic fraction in neon‐irradiated tumors was significantly higher than that in X‐irradiated tumors (69.53% vs. 47.67%). Simultaneously, the hypoxic fraction in neon‐ion‐irradiated tumors (2.77%) was lower than that in X‐irradiated tumors (4.27%) and non‐irradiated tumors (32.44%). These results support the notion that accelerated reoxygenation occurs more effectively with neon‐ion beam irradiation compared to X‐rays. These findings shed light on the physiological effects of neon‐ion beams on tumors and their microenvironment, emphasizing the therapeutic advantage of using neon‐ion charged particle beams to manipulate tumor reoxygenation. [ABSTRACT FROM AUTHOR]

Plastic change of the neuronal system has traditionally been assumed to be governed primarily by the long-term potentiation/depression mechanisms of synaptic transmission. However, a rather simple shift in the ambient ion, transmitter and metabolite concentrations could have a pivotal role in generating plasticity upon the physiological process of learning and memory. Local brain environment and metabolic changes could also be the cause and consequences of the pathogenesis leading to epilepsy. Governing of the local brain environment is the primal function of astrocytes. The metabolic state of the entire brain is strongly linked to the activity of the lateral hypothalamus. In this study, plastic change of astrocyte reactions in the lateral hypothalamus was examined using epileptogenesis as an extreme form of plasticity. Fluorescent sensors for calcium or pH expressed in astrocytes were examined for up to one week by in vivo fibre photometry in freely moving transgenic male mice. Optical fluctuations on a timescale of seconds is difficult to assess because these signals are heavily influenced by local brain blood volume changes and pH changes. Using a newly devised method for the analysis of the optical signals, changes in Ca2+ and pH in astrocytes and changes in local brain blood volume associated with hippocampal-stimulated epileptic seizures were extracted. Following a transient alkaline shift in the astrocyte triggered by neuronal hyperactivity, a prominent acidic shift appeared in response to intensified seizure which developed with kindling. The acidic shift was unexpected as transient increase in local brain blood volume was observed in response to intensified seizures, which should lead to efficient extrusion of the acidic CO2. The acidic shift could be a result of glutamate transporter activity and/or due to the increased metabolic load of astrocytes leading to increased CO2 and lactate production. This acidic shift may trigger additional gliotransmitter release from astrocytes leading to the exacerbation of epilepsy. As all cellular enzymic reactions are influenced by Ca2+ and pH, changes in these parameters could also have an impact on the neuronal circuit activity. Thus, controlling the astrocyte pH and/or Ca2+ could be a new therapeutic target for treatment of epilepsy or prevention of undesired plasticity associated with epileptogenesis. [ABSTRACT FROM AUTHOR]

Background: We recently developed a positron emission tomography (PET) probe, [18F]PM‐PBB3, to detect tau lesions in diverse tauopathies, including mixed three‐repeat and four‐repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias‐free quantitative evaluation of tau images without a priori disease information is needed. Objective: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities. Methods: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross‐validation linear classification analysis with a one‐versus‐the‐rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve. We defined PSP‐ and AD‐tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others. Results: The discriminatory ability of PSP‐ and AD‐tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSP‐tau scores correlated with the PSP rating scale in patients with PSP, and AD‐tau scores correlated with Mini‐Mental State Examination scores in healthy control–AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP‐ and AD‐tau scores, respectively. Conclusions: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]