δ-Opioid Receptors, microRNAs, and Neuroinflammation in Cerebral Ischemia/Hypoxia

Hypoxia and ischemia are the main underlying pathogenesis of stroke and other neurological disorders. Cerebral hypoxia and/or ischemia (e.g., stroke) can lead to neuronal injury/death and eventually cause serious neurological disorders or even death in the patients. Despite knowing these serious consequences, there are limited neuroprotective strategies against hypoxic and ischemic insults in clinical settings. Recent studies indicate that microRNAs (miRNAs) are of great importance in regulating cerebral responses to hypoxic/ischemic stress in addition to the neuroprotective effect of the δ-opioid receptor (DOR). Moreover, new discovery shows that DOR can regulate miRNA expression and inhibit inflammatory responses to hypoxia/ischemia. We, therefore, summarize available data in current literature regarding the role of DOR and miRNAs in regulating the neuroinflammatory responses in this article. In particular, we focus on microglia activation, cytokine production, and the relevant signaling pathways triggered by cerebral hypoxia/ischemia. The intent of this review article is to provide a novel clue for developing new strategies against neuroinflammatory injury resulting from cerebral hypoxia/ischemia.