The aim of the present study was to examine the neuroprotective effect of Qingnao dripping pills (QNDP), especially the infiltration of neutrophils and macrophages, as well as the mitogen-activated protein kinase (MAPK) signal pathway. Adult male Sprague-Dawley rats were randomized to three groups: sham, MCAO, and QNDP. After 24 h of ischemia and reperfusion, neurological deficit scores and infarct volume were measured. Macrophages and neutrophil infiltration in the ischemic brain were respectively determined with CD68 and MPO immunofluorescence and western blot. The proteins involved in MAPK signaling (SAPK/JNK, P-SAPK/JNK, p38, P-p38, ERK1/2, and P-ERK1/2) were measured by western blotting. In vitro ischemic paradigm (oxygen-glucose deprivation) was performed in SH-SY5Y cells to evaluate the effects of QNDP. The viability and death ration of cells induced OGD/R was measured by MTT and LDH assay. The proteins involved in MAPK signaling were measured by western blotting. The results showed that QNDP treatment significantly improved the neurological deficit scores and reduced infarct size. In addition, QNDP treatment inhibited the number of CD68- and MPO-positive cells in the ischemic brain. It inhibited the MAPK signaling pathway in the ischemic brain and SH- SY5Y cells induced OGD/R.

Exosomes are a type of extracellular vesicles secreted by almost all kinds of mammalian cells that shuttle “cargo” from one cell to another, indicative of its role in cell‐to‐cell transportation. Interestingly, exosomes are known to undergo alterations or serve as a pathway in multiple diseases, including neurodegenerative diseases. In the central nervous system (CNS), exosomes originating from neurons or glia cells contribute to or inhibit the progression of CNS‐related diseases in special ways. In lieu of this, the current study investigated the effect of CNS cell‐derived exosomes on different neurodegenerative diseases.

Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that in cerebral ischemia, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key mediator in mediating inflammatory responses and results in activation of apoptosis signaling pathways. Here we assessed the in vivo and in vitro effects of Qingnao Dripping Pills (QNDP), a traditional Chinese prescription, on inflammatory responses and apoptosis. Our results showed that QNDP could significantly decrease cerebral ischemia injury, improve neurological function and inhibit apoptosis in rats impaired by middle cerebral artery occlusion (MCAO). Further, we found that QNDP inhibited NLRP3 inflammasome expression both in MCAO rats and in SH-SY5Y cells under OGD. Moreover, the levels of inflammatory cytokines including interleukin-1β (IL-1β) and IL-18, which mediated by NLRP3 inflammasome and increased in MCAO rats, could be reduced by QNDP, suggesting that QNDP could protect the neurons against inflammation through a mechanism mediated by NLRP3 inflammasome. Nuclear factor-kappa B (NF-κB) was also involved in the anti-inflammatory effect of QNDP. In conclusion, QNDP had neuroprotective effects against cerebral ischemia via inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke.

BACKGROUND:Autophagy is characterized by the degradation of cellular components in autophagosomes. It plays a significant role in cerebral ischemic injury and has a complex functional connection with apoptosis. The neurovascular unit (NVU) is a struc...