Recent reports of functional and anatomical studies have provided evidence that aberrant neural connectivity lies at the heart of many mental disorders. Information related to neural networks has ...elucidated the nonlinear dynamical complexity in brain signals over a range of temporal scales. The recent advent of nonlinear analytic methods, which have served for the quantitative description of the brain signal complexity, has provided new insights into aberrant neural connectivity in many mental disorders. Although many studies have underpinned aberrant neural connectivity, findings related to complexity behavior are still inconsistent. This inconsistency might result from (i) heterogeneity in mental disorders, (ii) analytical issues, (iii) interference of typical development and aging. First, most mental disorders are heterogeneous in their clinical feature or intrinsic pathological mechanisms. Second, neurophysiologic output signals from complex brain connectivity might be characterized with multiple time scales or frequencies. Finally, age-related brain complexity changes must be considered when investigating pathological brain because typical brain complexity is not constant across generations. Future systematic studies addressing these issues will greatly expand our knowledge of neural connections and dynamics related to mental disorders.
Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or ...improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke. Microglia and monocytes/macrophages polarize to the classic pro-inflammatory type (M1-like) or alternative protective type (M2-like) by optimal condition. Cell-based therapies using M2-like microglia and monocytes/macrophages might be protective therapeutic strategies against stroke for three reasons. First, M2-like microglia and monocytes/monocytes secrete protective remodeling factors, thus prompting neuronal network recovery via tissue (including neuronal) and vascular remodeling. Second, these cells could migrate to the injured hemisphere through the blood-brain barrier or choroid-plexus. Third, these cells could mitigate the extent of inflammation-induced injuries by suitable timing of therapeutic intervention. Although future translational studies are required, M2-like microglia and monocytes/macrophages therapies are attractive for managing stroke based on their protective functions.
This review focuses on the mechanisms and emerging concepts of stroke and therapeutic strategies for attenuating hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment for ...acute ischemic stroke (AIS). The therapeutic time window for tPA treatment has been extended. However, the patients who are eligible for tPA treatment are still ＜5% of all patients with AIS. The risk of serious or fatal symptomatic hemorrhage increases with delayed initiation of treatment. HT is thought to be caused by 1) ischemia/reperfusion injury; 2) the toxicity of tPA itself; 3) inflammation; and/or 4) remodeling factor-mediated effects. Modulation of these pathophysiologies is the basis of direct therapeutic strategies to attenuate HT after tPA treatment. Several studies have revealed that matrix metalloproteinases and free radicals are potential therapeutic targets. In addition, we have demonstrated that the inhibition of the vascular endothelial growth factor-signaling pathway and supplemental treatment with a recombinant angiopoietin-1 protein might be a promising therapeutic strategy for attenuating HT after tPA treatment through vascular protection. Moreover, single-target therapies could be insufficient for attenuating HT after tPA treatment and improving the therapeutic outcome of patients with AIS. We recently identified progranulin, which is a growth factor and a novel target molecule with multiple therapeutic effects. Progranulin might be a therapeutic target that protects the brain through suppression of vascular remodeling (vascular protection), neuroinflammation, and/or neuronal death (neuroprotection). Clinical trials which evaluate the effects of anti-VEGF drugs or PGRN-based treatment with tPA will be might worthwhile.
Methylmercury (MeHg) causes severe damage to the central nervous system, and there is increasing evidence of the association between MeHg exposure and vascular dysfunction, hemorrhage, and edema in ...the brain, but not in other organs of patients with acute MeHg intoxication. These observations suggest that MeHg possibly causes blood-brain barrier (BBB) damage. MeHg penetrates the BBB into the brain parenchyma via active transport systems, mainly the l-type amino acid transporter 1, on endothelial cell membranes. Recently, exposure to mercury has significantly increased. Numerous reports suggest that long-term low-level MeHg exposure can impair endothelial function and increase the risks of cardiovascular disease. The most widely reported mechanism of MeHg toxicity is oxidative stress and related pathways, such as neuroinflammation. BBB dysfunction has been suggested by both in vitro and in vivo models of MeHg intoxication. Therapy targeted at both maintaining the BBB and suppressing oxidative stress may represent a promising therapeutic strategy for MeHg intoxication. This paper reviews studies on the relationship between MeHg exposure and vascular dysfunction, with a special emphasis on the BBB.
The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we ...examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments.
Cognitive functions produced by large-scale neural integrations are the most representative 'emergence phenomena' in complex systems. A novel approach focusing on the instantaneous phase difference ...of brain oscillations across brain regions has succeeded in detecting moment-to-moment dynamic functional connectivity. However, it is restricted to pairwise observations of two brain regions, contrary to large-scale spatial neural integration in the whole-brain. In this study, we introduce a microstate analysis to capture whole-brain instantaneous phase distributions instead of pairwise differences. Upon applying this method to electroencephalography signals of Alzheimer's disease (AD), which is characterised by progressive cognitive decline, the AD-specific state transition among the four states defined as the leading phase location due to the loss of brain regional interactions could be promptly characterised. In conclusion, our synthetic analysis approach, focusing on the microstate and instantaneous phase, enables the capture of the instantaneous spatiotemporal neural dynamics of brain activity and characterises its pathological conditions.
In these multiscale neural activities, the network dynamics, which is captured by the degree of synchronization and information flow between pair-wise brain regional neural activities called dynamic ...functional connectivity (dFC), play an important role in coordinating the mutual interactions of neural activities (reviewed in Cohen, 2018; Luppi et al., 2022). ...besides the pair-wise neural interactions, the temporal itinerancy of the global topology of the whole-brain functional network is present (Guan et al., 2022). Subsequently, a more rigid method for determining the length of a window based on the temporal transition of a quasistable spatial power distribution, called a microstate, was proposed (Guan et al., 2022; Yan et al., 2023). ...instead of focusing on synchronization within the time-window, a technique of utilizing the instantaneous temporal patterns produced by neural interaction was also developed, which is required for achieving high temporal resolution to capture the characteristics of moment-to-moment dynamical functional connectivity (Nobukawa et al., 2019). Recent mathematical modeling of brain networks focuses on large hierarchical neural characteristics from the molecular/cellular and local neural circuit levels to the global whole brain level. ...embedding disease-specific impairments into the modeled-brain network studies could reveal the mechanisms by which these individual impairments affect the alternations of brain network dynamics (Matsumoto et al., 2023; Park et al.; Zhu et al.). Network dynamics in the physiological-data approach Studies in this decade have revealed that functional connectivity exhibits large temporal variability, even in the resting state, which is called dFC (Betzel et al., 2012; Hutchison et al., 2013; Allen et al., 2014; Calhoun et al., 2014; Hansen et al., 2015) (reviewed in Cohen, 2018).
Background: The prognosis of peripheral artery disease (PAD) and comorbid sarcopenia is poor. Some reports indicate that the computed tomography (CT) value of skeletal muscle, which reflects ...intramuscular fat deposition as well as skeletal muscle mass, is considered a marker of sarcopenia. However, it remains unclear if skeletal muscle area and CT value are associated with poor outcomes in patients with PAD. Methods and Results: Psoas muscle area and CT value were measured by manual trace at the level of the third lumbar vertebral body in 327 consecutive patients with PAD undergoing endovascular therapy (EVT). The endpoint was major adverse cardiovascular and limb events (MACLE). There were 60 MACLE during the follow-up period. Patients with MACLE had lower mean psoas muscle CT value than those without. However, there was no significant difference in total psoas muscle area between patients with and without MACLE. Kaplan-Meier analysis demonstrated that the lowest tertile of psoas muscle CT value was associated with the highest risk of MACLE. Multivariate Cox hazard analysis revealed that psoas muscle CT value was associated with MACLE after adjustment for Fontaine class, previous ischemic heart disease, prevalence of diabetes mellitus, brain natriuretic peptide, and serum albumin. Conclusions: Psoas muscle CT value is a feasible predictor of MACLE in patients with PAD.
【Aim】 To identify factors in deciding on the indications for and timing of surgery for blunt intestinal damage. 【Subjects and Methods】 The subjects were patients with blunt injury suspected of having ...intestinal damage based on the CT findings on arrival at our hospital, and we retrospectively attempted to identify factors in deciding on the indications for and timing of surgery. 【Results】 There were 36 patients:10 in an emergency surgery group, 6 in an elective surgery group, and 20 in a conservative treatment group. The most common site of intestinal damage was the small intestine. There was a significant difference in the number of abnormal CT findings between the emergency surgery group plus elective surgery group and conservative treatment group （3.1±1.2 vs. 2.0±0.9, P<0.01） and between the emergency surgery group and the elective surgery group （3.6±1.1 vs. 2.2±0.8, P<0.01）. 【Conclusion】 The number of abnormal findings on the CT examination on arrival at the hospital appeared to be an important factor in deciding on the indications for and the timing of surgery.
Alzheimer's disease (AD) is the most common form of dementia and is a progressive neurodegenerative disease that primarily develops in old age. In recent years, it has been reported that early ...diagnosis of AD and early intervention significantly delays disease progression. Hence, early diagnosis and intervention are emphasized. As a diagnostic index for AD patients, evaluating the complexity of the dependence of the electroencephalography (EEG) signal on the temporal scale of Alzheimer's disease (AD) patients is effective. Multiscale entropy analysis and multifractal analysis have been performed individually, and their usefulness as diagnostic indicators has been confirmed, but the complemental relationship between these analyses, which may enhance diagnostic accuracy, has not been investigated. We hypothesize that combining multiscale entropy and fractal analyses may add another dimension to understanding the alteration of EEG dynamics in AD. In this study, we performed both multiscale entropy and multifractal analyses on EEGs from AD patients and healthy subjects. We found that the classification accuracy was improved using both techniques. These findings suggest that the use of multiscale entropy analysis and multifractal analysis may lead to the development of AD diagnostic tools.
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