Lowering temperature rapidly reduced p38 activation and the subsequent p38-regulated production of pro-inflammatory cytokines and NO in ATP-activated microglia, suggesting that attenuation of early phase inflammatory responses via suppression of p38 in microglia is one possible neuroprotective mechanism of therapeutic hypothermia. Temperature elevation increased TNF-α and NO production in these cells. These temperature-dependent changes imply that monitoring of TNF-α and NO in the cerebrospinal fluid during the early phase might be useful as biomarkers for responses to therapeutic hypothermia and hyperthermia.

Hypothermic culture at 35 °C decreased the production of early-phase TNF-α and late-phase IL-10 and NO from ATP- and TLR-activated microglia as observed at 33 °C, albeit with diminished effects. Moreover, these factors caused the death of neuronal cells in a concentration-dependent manner. These results suggest that the attenuation of microglial production of TNF-α, IL-10, and NO by therapeutic hypothermia leads to the inhibition of neuronal cell death. Minimal hypothermia at 35 °C may be sufficient to elicit neuroprotective effect.

In this longitudinal intervention study, a 6 week health education program consisting of lectures and exercises was implemented for 39 Japanese menopausal women. The effects of the program were assessed by measuring their exercise participation, climacteric symptoms, and quality of life immediately before, 6 weeks after, and 1 year after the program. The Simplified Menopausal Index was used to assess the climacteric symptoms and the Medical Outcomes Study 36-Item Short-Form Health (SF-36) Survey was used to assess the quality of life. Significant improvements were observed in the subscale score for general health perception and the summary score for the physical component summary in the SF-36 Survey. Favorable results also were found for women without a previous exercise habit before the program but who participated in regular exercise 1 year after the program. No improvements were observed in the climacteric symptoms. We concluded that our program was effective for menopausal women in spite of the intervention period being relatively short.

Depression-like behavior is often complicated by chronic pain. Antidepressants including imipramine (IMI) are widely used to treat chronic pain, but the mechanisms are not fully understood. Brain-derived neurotrophic factor (BDNF) is a neuromodulator that reduces depression by regulating synaptic transmission. We aimed to characterize the antidepressant effects of IMI without analgesia based on BDNF (trkB)-mediated signaling and gene expression in chronic pain. A chronic constriction injury (CCI) model was constructed in Sprague-Dawley (SD) rats. IMI (5 mg/kg, i.p.) was administered from day 10 after CCI. The pain response was assessed using the paw withdrawal latency (PWL) and depression was judged from the immobility time in a forced swim test. Anti-BDNF antibody, K252a, or 5,7-dihydroxytryptamine (5,7-DHT) were used to examine the antidepressant effects of imipramine. Changes in pERK1/2 (immunohistochemistry), 5-HT and BDNF (ELISA), and BDNF mRNA (RT-PCR) were measured in the anterior cingulate cortex (ACC), rostral ventromedial medulla (RVM), and spinal cord. After CCI, rats showed decreased PWL and increased immobility time. A low dose of IMI reduced the immobility time without having analgesic effects. This antidepressant effect was reversed by anti-BDNF antibody, K252a, and 5,7-DHT. IMI reduced excessive activation of pERK1/2 associated with decreased pCREB and BDNF mRNA, and these changes were reversed by 5,7-DHT. These results show that IMI reduces pain-related negative emotion without influencing pain and that this effect is diminished by denervation of 5-HT neurons and by anti-BDNF treatment. IMI also normalizes derangement of ERK/CREB coupling, which leads to induction of BDNF. This suggests a possible interaction between 5-HT and BDNF.

Spending time in nature might positively influence mental health by inducing a relaxed state. Recently, gardens have been created on hospital rooftops in Japan to help inpatients recover from various physical and mental aliments. However, there is little evidence regarding any positive physiological effects of artificial gardens designed for health. The purpose of this study was to assess the psychological and cardiovascular responses incited by artificial natural environments. Japanese university students (n = 38) participated in a one-group pretest post-test experiment conducted at the Yamaguchi Flower Expo in Japan in October 2018, designed to assess whether exposure to four environments (forest, flowers, ocean, and artificial garden for health) influenced heart rate variability measures. After pretesting to determine baseline measurements, participants completed a circuit through the four natural environments. Following circuit completion, post-testing determined that the low frequency/high frequency ratio was significantly lower in the overall sample and the four areas had similar influences on heart rate variability. Findings suggest that exposure to nature by walking through natural areas and in rooftop artificial gardens might enhance the balance between the sympathetic and parasympathetic nervous systems.