Background: Stroke not only impacts patients physically but also economically. Post-stroke depression (PSD), as a common complication of stroke, always obstructs the process of stroke rehabilitation. Accordingly, defining the risk factors associated with PSD has extraordinary importance. Although there have been many studies investigating the risk factors for PSD, the results are inconsistent. Objectives: The objectives of this study were to identify the risk factors for PSD by evidence-based medicine. Data sources: A systematic and comprehensive database search was performed of PubMed, Medline, CENTRAL, EMBASE.com, the Cochrane library and Web of Science for Literature, covering publications from January 1, 1998 to November 19, 2016. Study Selection: Studies on risk factors for PSD were identified, according to inclusion and exclusion criteria. The risk of bias tool, described in the Cochrane Handbook version 5.1.0, was used to assess the quality of each study. Meta-analysis was performed using RevMan 5.3 software. Results: Thirty six studies were included for review. A history of mental illness was the highest ranking modifiable risk factor; other risk factors for PSD were female gender, age (<70y), neurotism, family history, severity of stroke, and level of handicap. Social support was a protective factor for PSD. Conclusion: There are many factors that have effects on Post-stroke depression. The severity of stroke is an important factor in the occurrence of PSD. Mental history is a possible predictor of PSD. Prevention of PSD requires social and family participation.

Background: Chronic pain conditions impose significant burdens worldwide. Pharmacological treatments like opioids have limitations. Non-invasive non-pharmacological therapies (NINPT) encompass diverse interventions including physical, psychological, complementary and alternative approaches, and other innovative techniques that provide analgesic options for chronic pain without medications.Main body: This review elucidates the mechanisms of major NINPT modalities and synthesizes evidence for their clinical potential across chronic pain populations. NINPT leverages peripheral, spinal, and supraspinal mechanisms to restore normal pain processing and limit central sensitization. However, heterogeneity in treatment protocols and individual responses warrants optimization through precision medicine approaches.Conclusion: Future adoption of NINPT requires addressing limitations in standardization and accessibility as well as synergistic combination with emerging therapies. Overall, this review highlights the promise of NINPT as a valuable complementary option ready for integration into contemporary pain medicine paradigms to improve patient care and outcomes.

Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer's disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect. Additionally, FoxO3a, a downstream member of the PI3K/AKT pathway, could be activated by TREM2 defect via the PI3K/AKT signaling in 5xFAD mice. That suggests TREM2-induced protection is associated with the PI3K-FoxO3a axis. On the contrary, overexpression of TREM2 alleviated the LPS-induced inflammatory response and induced M2 phenotype microglia in vitro. This phenomenon can be abolished by applying the PI3K inhibitor LY294002, suggesting FoxO3a not only participates in TREM2-induced anti-inflammation response, but is also involved in regulating the phenotype of microglia. Taken together, our results show that the protective functions of TREM2, both in inflammatory response and cognitive impairment as well as in the decrease of M1 phenotype microglia, are related to PI3K/AKT/FoxO3a signaling pathway in AD mice.

Background: Neuropathic pain (NeuP) is a chronic and challenging clinical problem, with little effective treatment. Resveratrol has shown neuroprotection by inhibiting inflammatory response in NeuP. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2) expressed by microglia was identified as a critical factor of inflammation in nervous system diseases. In this study, we explored whether resveratrol could ameliorate neuroinflammation and produce anti-mechanical allodynia effects via regulating TREM2 in spared nerve injury rats, as well as investigated the underlying mechanisms. Methods: A spared nerve injury (SNI) rat model was performed to investigate whether resveratrol could exert anti-mechanical allodynia effects via inhibiting neuroinflammation. To evaluate the role of TREM2 in anti-neuroinflammatory function of resveratrol, lentivirus coding TREM2 was intrathecally injected into SNI rats to activate TREM2, and the pain behavior was detected by the von Frey test. Furthermore, 3-methyladenine (3-MA, an autophagy inhibitor) was applied to study the molecular mechanisms of resveratrol-mediated anti-neuroinflammation using Western blot, qPCR, and immunofluorescence. Results: The TREM2 expression and number of the microglial cells were significantly increased in the ipsilateral spinal dorsal horn after SNI. We found that intrathecal administration of resveratrol (300ug/day) alleviated mechanical allodynia; obviously enhanced autophagy; and markedly reduced the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ipsilateral spinal dorsal horn after SNI. Moreover, the number of Iba-1⁺ microglial cells and TREM2 expression were downregulated after resveratrol treatment. Intrathecal administration of lentivirus coding TREM2 and/or 3-MA in those rats induced deficiencies in resveratrol-mediated anti-inflammation, leading to mechanical allodynia that could be rescued via administration of Res. Furthermore, 3-MA treatment contributed to TREM2-mediated mechanical allodynia. Conclusions: Taken together, these data reveal that resveratrol relieves neuropathic pain through suppressing microglia-mediated neuroinflammation via regulating the TREM2-autophagy axis in SNI rats.

Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.

Post stroke depression (PSD) is a serious complication of stroke. Brain imaging is an important method of studying the mechanism of PSD. However, few studies have focused on the single lesion location. The aim of this study was to investigate the brain mechanism of frontal lobe PSD using combined voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI). In total, 30 first-time ischemic frontal lobe stroke patients underwent T1 weighted MRI and resting-state fMRI scans. Clinical assessments included the 24-item Hamilton Rating Scale for Depression, the National Institutes of Health Stroke Scale, and the Mini-Mental State Examination. In our result, decreased gray matter (GM) volume in patients was observed in the prefrontal cortex, limbic system and motor cortex. The anterior cingulate cortex, selected as a seed to perform connectivity analyses, showed a greatly decreased functional connectivity with the prefrontal cortex, cingulate cortex, and motor cortex, but had an increased functional connectivity with the hippocampus gyrus, parahippocampa gyrus, insular, and amygdala. Stroke lesion location reduces excitability of brain areas in the ipsilateral brain. PSD affects mood through the brain network of the prefrontal-limbic circuit. Some brain networks, including motor cortex and the default mode network, show other characteristics of PSD brain network.