Experimental Psychology Its Scope and Method. IV. Learning and Memory. By Jean-Francois Le Ny, G. De Montpellier, G. Oleron and Cesar Flores. Translated by Louise Elkington. Edited by P. Fraisse and Jean Piaget. Pp. viii + 376. (Routledge and Kegan Paul: London, April 1970.) 80s.

Learning and Memory

Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of IL-1β and IL-18. While wild type Salmonella typhimurium infection is lethal to mice, a strain that persistently expresses flagellin was cleared by the cytosolic flagellin detection pathway via NLRC4 activation of caspase-1; however, this clearance was independent of IL-1β and IL-18. Instead, caspase-1 induced pyroptotic cell death released bacteria from macrophages, exposing them to uptake and killing by reactive oxygen species in neutrophils. Similarly, caspase-1 cleared Legionella and Burkholderia by cytokine independent mechanisms. Our results show, for the first time, that caspase-1 can clear intracellular bacteria in vivo independent of IL-1β and IL-18, and establish pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.

Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (111.33)

https://academicworks.medicine.hofstra.edu/cgi/viewcontent.cgi?article=1534&context=articles

HMGB1 in Health and Disease

Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise

Pathological pain and the neuroimmune interface

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there are few therapeutics that affect the underlying disease mechanism. Recent epidemiological studies, however, suggest that lifestyle changes may slow the onset/progression of AD. Here we have used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade. Five months of voluntary exercise resulted in a decrease in extracellular amyloid-β (Aβ) plaques in the frontal cortex (38%; p = 0.018), the cortex at the level of the hippocampus (53%; p = 0.0003), and the hippocampus (40%; p = 0.06). This was associated with decreased cortical Aβ1-40 (35%; p = 0.005) and Aβ1-42 (22%; p = 0.04) (ELISA). The mechanism appears to be mediated by a change in the processing of the amyloid precursor protein (APP) after short-term exercise, because 1 month of activity decreased the proteolytic fragments of APP [for α-C-terminal fragment (α-CTF), 54% and p = 0.04; for β-CTF, 35% and p = 0.03]. This effect was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, may involve neuronal metabolism changes that are known to affect APP processing and to be regulated by exercise. Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant (p < 0.02) reductions in escape latencies over the first 3 (of 6) trial days. In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.

Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's diseases

Ischemic postconditioning protects brain from ischemia/reperfusion injury by attenuating endoplasmic reticulum stress-induced apoptosis through PI3K-Akt pathway

The management of neuropathic pain is still a major challenge because of its unresponsiveness to most common treatments. Curcumin has been reported to play an active role in the treatment of various neurological disorders, such as neuropathic pain. Curcumin has long been recognized as a p300/CREB-binding protein (CBP) inhibitor of histone acetyltransferase (HAT) activity. However, this mechanism has never been investigated for the treatment of neuropathic pain with curcumin. The aim of the present study was to investigate the anti-nociceptive role of curcumin in the chronic constriction injury (CCI) rat model of neuropathic pain. Furthermore, with this model we investigated the effect of curcumin on P300/CBP HAT activity-regulated release of the pro-nociceptive molecules, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (Cox-2). Treatment with 40 and 60 mg/kg body weight curcumin for 7 consecutive days significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, whereas 20 mg/kg curcumin showed no significant analgesic effect. Chromatin immunoprecipitation analysis revealed that curcumin dose-dependently reduced the recruitment of p300/CBP and acetyl-Histone H3/acetyl-Histone H4 to the promoter of BDNF and Cox-2 genes. A similar dose-dependent decrease of BDNF and Cox-2 in the spinal cord was also observed after curcumin treatment. These results indicated that curcumin exerted a therapeutic role in neuropathic pain by down-regulating p300/CBP HAT activity-mediated gene expression of BDNF and Cox-2.

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Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model

OBJECTIVES Enhanced recovery after surgery (ERAS) pathways have not been reported in cardiac surgery. The aim of this study was to evaluate the clinical effectiveness and safety profile of ERAS pathways compared with routine care for patients undergoing cardiac valvular surgery. METHODS A randomized clinical trial was conducted between July 2015 and November 2016. A total of 226 patients who underwent elective valvular surgery were randomly assigned to the ERAS pathway or routine care (control) group. The ERAS protocol consisted of an evidence-based systematic optimization approach for managing perioperative patients. The control group received routine care. The primary end-point was readiness for hospital discharge. The secondary outcomes were duration of intensive care unit (ICU) stay, length of postoperative vasoactive drug support, duration of mechanical ventilation, time to first bowel movement, removal of surgical drain, overall medical costs and complication rate. RESULTS Postoperative time to readiness for discharge was significantly shorter in the ERAS group (6.0 (2.0∼14.0) days) than the control group (7.0 (4.0∼16.0) days, P = 0.01), and the duration of ICU stay and duration of mechanical ventilation were significantly shorter in the ERAS group (20.9 (13.5∼69.3) h, 7.2 (0.0∼22.3) h, respectively) than the control group (22.0 (13.4∼212.3) h, P = 0.001; 8.8 (3.7∼44.9) h, respectively; P < 0.0001). The overall treatment cost of the ERAS group (69202 (52089∼123823) CNY) was significantly lower than that of the control group (77058 (51390∼144290) CNY, P = 0.002). CONCLUSIONS ERAS pathways reduce the length of ICU and hospital stay, postoperative complications and cost for patients undergoing cardiac surgery. Clinical trial registration ClinicalTrials.gov: NCT02479581.

Enhanced recovery after surgery pathway for patients undergoing cardiac surgery: a randomized clinical trial.

Intrathecal 5-azacytidine inhibits global DNA methylation and methyl- CpG-binding protein 2 expression and alleviates neuropathic pain in rats following chronic constriction injury

Qulian Guo

Papers

Ischemic postconditioning protects brain from ischemia/reperfusion injury by attenuating endoplasmic reticulum stress-induced apoptosis through PI3K-Akt pathway

Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model

Enhanced recovery after surgery pathway for patients undergoing cardiac surgery: a randomized clinical trial.

Intrathecal 5-azacytidine inhibits global DNA methylation and methyl- CpG-binding protein 2 expression and alleviates neuropathic pain in rats following chronic constriction injury

Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats.