English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Microglia are the principle mediators of neuroinflammation, as defined by increased expression of pro-inflammatory cytokines such as TNF-a, IL-1b and IL-6. Two patient populations, young and aged, are at significant risk for behavioural and cognitive impairments after isoflurane exposure. Evidence indicates that neuroinflammation may be one of the causative events leading to neuronal and synaptic loss. The aim of this review was to discuss how microglia provide unexplored avenues to attenuate cognitive decline following isoflurane exposure in susceptible young and elderly patients. Conclusion Isoflurane exposure affects the actin cytoskeleton in neurons and astrocytes, but cytoskeletal effects from isoflurane exposure have not been well studied in microglia. TREM2 expression, a known inflammatory and cytoskeletal regulating protein, is reduced in young and aged population leading to depression of microglia phagocytosis and increased inflammation. Therefore, modulation of upstream or downstream TREM2mediated signalling may be a route to attenuate cognitive impairments in both populations. Introduction Learning disabilities and behavioural issues in children and post-operative cognitive decline (POCD) in elderly patients after anaesthetic exposure pose a significant health issue adding extra pressure to often already overburdened school systems and long-term care facilities. A major risk factor for childhood development of testable cognitive impairment is multiple exposures of inhaled anaesthetics. Wilder et al. have defined a specific subpopulation of children at particular risk for long-term learning disabilities: children below the age of four who incur at least three surgical exposures1. In the elderly, POCD aetiology may involve multiple factors, such as nutritional states and metabolic states or the type of surgical procedure2. A majority of potential therapies or interventions currently being explored are aimed at attenuating neuronal apoptosis and synaptic loss or increasing neurotrophic survival factors such as the brain derived neurotrophic factor (BDNF)3. A recent review of 25 randomized clinical trials of neuroprotective pharmacological compounds including: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/ aspartate, Xenon, remacemide, atorvastatin and magnesium sulphate, found all but three were ineffective at preventing POCD when compared to controls. Lidocaine, S(+)-ketamine and magnesium sulphate had inconclusive results4. The inert noble gas Xenon has been proposed as a prophylactic treatment for ISO exposure during mouse surgeries. Pre-treatment of 70% Xenon for 20 minutes followed by 1.8% ISO during surgery reduced serum IL-1b levels but mice cognitive abilities were only tested post surgery P15. A novel approach to preventing POCD through activation of autophagic pathways with rapamycin to inhibit mTOR has been proposed6. But this approach is limited to use in an aged population, as increased autophagy is associated with increased neuronal apoptosis after ischemic injury in neonatal rat experiments7. In this critical review, we propose a more focused therapeutic target to explore. Microglia, required to resolve neuroinflammatory states and modulation to a phagocytic phenotype without inducing neuroinflammation, could provide neuroprotection. The expression of triggering receptor expressed in myeloid cells 2 (TREM2) is reduced in microglia during the anaesthetic sensitive period in young8 and in aged rodents9. This reduction is associated with decreased phagocytosis and increased inflammation. Due to the biphasic expression pattern and clear function in CNS homeostasis, we believe TREM2 signalling is an intriguing pharmacological target to attenuate childhood learning and behavioural impairments and POCD in aged patients caused by ISO exposure.

oa anaesthetics

Microglia provide unexplored avenues to attenuate cognitive decline following isoflurane exposure in susceptible young and elderly patients: A critical review of TREM2-DAP12 function and therapeutic potential