Inflammatory response contributes to brain injury after ischemia and reperfusion (I/R). Our previous literature has shown isoquercetin plays an important role in protecting against cerebral I/R injury. The present study was conducted to further investigate the effect of isoquercetin on inflammation-induced neuronal injury in I/R rats with the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and inhibitor of NF-κB (I-κB)/nuclear factor-kappa B (NF-κB) signaling pathway mediated by Toll-like receptor 4 (TLR4) and C5a receptor 1 (C5aR1). In vivo middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation and reperfusion (OGD/R) neuron model were used. MCAO/R induced neurological deficits, cell apoptosis, and release of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in ischemic brain in rats. Simultaneously, the expression of TLR4 and C5aR1 was significantly up-regulated in both MCAO/R rats and OGD/R neurons, accompanied with the inhibition of cAMP/PKA signaling and activation of I-κB/NF-κB signaling in the cortex of MCAO/R rats. Over-expression of C5aR1 in neurons induced decrease of cell viability, exerting similar effects with OGD/R injury. Isoquercetin acted as a neuroprotective agent against I/R brain injury to suppress inflammatory response and improve cell recovery by inhibiting TLR4 and C5aR1 expression, promoting cAMP/PKA activation, and inhibiting I-κB/NF-κB activation and Caspase 3 expression. TLR4 and C5aR1 contributed to inflammation and apoptosis via activating cAMP/PKA/I-κB/NF-κB signaling during cerebral I/R, suggesting that this signaling pathway may be a potent therapeutic target in ischemic stroke. Isoquercetin was identified as a neuroprotective agent, which maybe a promising therapeutic agent used for the treatment of ischemic stroke and related diseases.

Radiotherapy is one of the primary modalities for oncologic treatment and has been utilized at least once in over half of newly diagnosed cancer patients. Cranial radiotherapy has significantly enhanced the long-term survival rates of patients with brain tumors. However, radiation-induced brain injury, particularly hippocampal neuronal damage along with impairment of neurogenesis, inflammation, and gliosis, adversely affects the quality of life for these patients. Astrocytes, a type of glial cell that are abundant in the brain, play essential roles in maintaining brain homeostasis and function. Despite their importance, the pathophysiological changes in astrocytes induced by radiation have not been thoroughly investigated, and no systematic or comprehensive review addressing the effects of radiation on astrocytes and related diseases has been conducted. In this paper, we review current studies on the neurophysiological roles of astrocytes following radiation exposure. We describe the pathophysiological changes in astrocytes, including astrogliosis, astrosenescence, and the associated cellular and molecular mechanisms. Additionally, we summarize the roles of astrocytes in radiation-induced impairments of neurogenesis and the blood-brain barrier (BBB). Based on current research, we propose that brain astrocytes may serve as potential therapeutic targets for treating radiation-induced brain injury (RIBI) and subsequent neurological and neuropsychiatric disorders.