ABSTRACT
Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte-specific ADORA2B (eAdora2b-/-) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b-/- mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B-BPGM axis is a key component for anti-aging and anti-age-related functional decline.
Subject(s)
Auditory Pathways/physiopathology , Cognitive Dysfunction/metabolism , Erythrocytes/metabolism , Hypoxia/metabolism , Receptor, Adenosine A2B/metabolism , 2,3-Diphosphoglycerate/metabolism , Aging/pathology , Animals , Bisphosphoglycerate Mutase/genetics , Bisphosphoglycerate Mutase/metabolism , Brain/pathology , Brain/physiopathology , Cochlea/physiopathology , Cognitive Dysfunction/complications , Cognitive Dysfunction/genetics , Cognitive Dysfunction/physiopathology , Enzyme Activation , Gene Deletion , Glycolysis , Hypoxia/complications , Hypoxia/genetics , Hypoxia/physiopathology , Inflammation/complications , Inflammation/pathology , Inflammation Mediators/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , Microglia/metabolism , Microglia/pathology , Receptor, Adenosine A2B/deficiencyABSTRACT
The objective of this study is to evaluate possible prognostic factors of idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From January 2008 to October 2016, records of 178 ISSNHL patients treated with auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and evaluate associated prognostic factors (gender, age, localization, initial hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension, diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and multivariate analyses. The overall recovery rate was 37.1%, including complete recovery (19.7%) and partial recovery (17.4%). According to multivariate analysis, later onset of HBOT and higher initial hearing threshold were associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is possibly enough to show its therapeutic effect. Earlier HBOT onset and lower initial hearing threshold is associated with favorable hearing recovery.
Subject(s)
Hearing Loss, Sensorineural/therapy , Hearing Loss, Sudden/therapy , Hyperbaric Oxygenation , Adolescent , Adult , Aged , Child , Combined Modality Therapy , Female , Follow-Up Studies , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sudden/diagnosis , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Young AdultABSTRACT
CONCLUSIONS: Intratympanic steroid (ITS) treatment groups exhibited better outcomes in PTA improvement and recovery rate than systemic steroid therapy (SST) groups. Whether initial hearing loss severity would influence the PTA improvement and recovery rate still requires further research. OBJECTIVE: This article was aimed at evaluating whether intratympanic steroid (ITS) treatment would provide benefits over systemic steroid therapy (SST) as initial therapy in patients with idiopathic sudden sensorineural hearing loss (ISSHL). A meta-analysis was carried out based on published RCTs that included the hearing outcomes of ITS treatment and SST in ISSHL as initial therapy. Both PTA differences and recovery rate were analyzed. METHODS: The literature search was based on the online database including Pubmed, Embase, and Cochrane trails, which completed in July 2016. This study extracted the relevant data following the selection criteria. Mean difference (MD) of PTA differences and Odds ratio (OR) of recovery rate were calculated within 95% confidence intervals. RESULTS: Six eligible articles were reviewed. The pooled MDs of PTA differences was 3.42 (95% CI = 0.17-6.67, p = .04) and the pooled ORs of recovery rate was 2.05 (95% CI = 1.38-3.03, p = .0003), which indicated that ITS treatment yielded better PTA improvement than SST. Sub-group analyses based on the initial hearing loss were also conducted; however, the difference was insignificant according to our analysis results (p = .82 for PTA improvement and p = .26 for recovery rate).
