Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone

Abstract

Allergic asthma is a typical chronic inflammatory disease of respiratory tract. Clinical data shows that patients with allergic asthma have different degrees of cognitive dysfunction. The molecular mechanism underlying the pathogenesis of asthma-induced cognitive disorder is not yet well defined. Dexamethasone (DEX), one of the first-line drugs being widely used in the treatment of asthma, has not been reported to have an effect on cognitive dysfunction in mice model. To investigate the effect of asthma on cognitive impairment as well as the effect of DEX on asthma-caused morphological and behavioral changes, C57BL/6J mice received treatment with house dust mites (HDM) for 60 days to become allergic asthma model mice, and a group of HDM-treated asthma model mice were treated with DEX. HDM-treated asthma model mice exhibited increased airway hyperresponsiveness (AHR) and inflammatory infiltration in lung tissue. An elevated level of IL-4, IL-5, and TNF-α was detected in bronchoalveolar lavage fluid (BALF) by Luminex liquid suspension chip. Asthma model mice also presented memory deficits accompanied with morphological changes at the synaptic levels in the cortex and hippocampus. Meanwhile, vascular edema and increased expression of HIF-1α and HIF-2α were found in the brain of asthma model mice. Interestingly, DEX treatment could reverse the inflammatory changes in asthma model mice airway, rescue the cognitive impairment and improve the synaptic plasticity. Besides, DEX significantly decreased the expression of HIF-1α and HIF-2α in mice brain and lung. These processes may be used to decipher the complex interplay and pathological changes between asthma and cognition. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction induced by asthma.

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

“…AHR is a typical symptom of asthma that can also be associated with behavioral changes in mice ( 38 ). In the present study, following intranasal administration of OVA, mice in the OVA group were more irritated and exhibited an elevated respiratory rate, compared with the OVA + DEX group.…”

Identifying latent comorbidity patterns in adults with perceived cognitive impairment: Network findings from the behavioral risk factor surveillance system

“…On the other hand, some mechanisms underlying the association between asthma and respiratory diseases with cognitive impairment have been suggested. Prominent among these mechanisms are the fact that asthma causes aberrations of synaptic tissues and blood vessels, elevated levels of hypoxia-inducible factor-1alpha (HIF-1α) and hypoxia-induced factor-2α (HIF-2α) ( 42 ). Based on this phenomenon, it is suggested that asthma may cause oxygen deprivation and eventually lead to cognitive impairment ( 42 ).…”

“…Prominent among these mechanisms are the fact that asthma causes aberrations of synaptic tissues and blood vessels, elevated levels of hypoxia-inducible factor-1alpha (HIF-1α) and hypoxia-induced factor-2α (HIF-2α) ( 42 ). Based on this phenomenon, it is suggested that asthma may cause oxygen deprivation and eventually lead to cognitive impairment ( 42 ). These findings imply that, during clinical evaluations of cognitive impairment, patients with this pathology should also be evaluated to detect diseases, such as arthritis, asthma, respiratory diseases, and depression; although it is not a standard practice in the clinical evaluation of perceived cognitive impairment.…”

Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma

“…We have reported that exposure to environmental chemicals enhanced these effects [ 12 , 13 , 14 ]. A recent study has also demonstrated that asthma-induced brain hypoxia caused the impairment of learning and memory via dysfunction of synaptic tissues and blood vessels, increased levels of hypoxia-inducible factors marker Hif-1α and Hif-2α [ 15 ]. Therefore, in this study, we hypothesized that chemical alone, asthma alone, or co-exposure of chemical and allergen induces brain hypoxia causes memory impairment via modulation of hippocampal synaptic genes and inflammatory mediators released from brain immune and glial cells.…”