Vagus nerve stimulation protects against cerebral injury after cardiopulmonary resuscitation by inhibiting inflammation through the TLR4/NF-κB and α7nAChR/JAK2 signaling pathways

BACKGROUND: Our previous research proved that vagus nerve stimulation(VNS) improved the neurological outcome after cardiopulmonary resuscitation(CPR) by activating α7 nicotinic acetylcholine receptor(α7nAChR) in a rat model, but the underlying mechanism of VNS in neuroprotection after CPR remains unclear.METHODS: In vivo, we established a mouse model of cardiac arrest(CA)/CPR to observe the survival rate, and the changes in inflammatory factors and brain tissue after VNS treatment. In vitro, we examined the effects of α7nAChR agonist on ischemia/reperfusion(I/R)-induced inflammation in BV2 cells under oxygen-glucose deprivation/reoxygenation(OGD/R) conditions. We observed the changes in cell survival rate, the levels of inflammatory factors, and the expressions of α7nAChR/Janus kinase 2(JAK2) and toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB).RESULTS: In vivo, VNS preconditioning enhanced functional recovery, improved the survival rate, and reduced hippocampal CA1 cell damage, and the levels of inflammatory mediators after CA/CPR. The application of α7nAChR agonists provided similar effects against cerebral injury after the return of spontaneous circulation(ROSC), while α7nAChR antagonists reversed these neuroprotective impacts. The in vitro results mostly matched the findings in vivo. OGD/R increased the expression of tumor necrosis factor-alpha(TNF-α), TLR4 and NF-κB p65. When nicotine was added to the OGD/R model, the expression of TLR4, NF-κB p65, and TNF-α decreased, while the phosphorylation of JAK2 increased, which was prevented by preconditioning with α7nAChR or JAK2 antagonists.CONCLUSION: The neuroprotective effect of VNS correlated with the activation of α7nAChR. VNS may alleviate cerebral IR injury by inhibiting TLR4/NF-κB and activating the α7nAChR/JAK2 signaling pathway.

Prey decline leads to diet shift in the largest population of Indo-Pacific humpback dolphins?

The Pearl River Delta(PRD)region on the southeast coast of China has long been known as a highly productive fishing ground.Since the late 1980s,fishing pressure in the PRD has been intense,which warrants concerns of potential fishery-related impacts on the food resources and foraging ecology of apex marine predators in this region,such as the Indo-Pacific humpback dolphin(Sousa chinensis).In this study,we examined 54 stomachs with food remains,collected from beached carcasses of humpback dolphins recovered during fifteen years between 2003 and 2017.The 6043 identified prey items represent 62 teleost taxa,primarily small estuarine fish,but also larger reef fish.The dolphins appear to be opportunistic foragers,hunting across the water-column,with preference for shoaling and meaty fishes(e.g.Collichthys lucidus IRI%=38.6%,Johnius belangerii IRI%=23.1%,Mugil cephalus IRI%=14.0%).Our findings suggest a dietary shift in recent years,from primarily demersal(as previously reported)to greater intake of neritic and pelagic fish.Dolphin foraging group size has decreased in recent years,which corresponds with declining size and numbers of prey items retrieved from dolphin stomachs.We suggest that these are indicators of declining food resources.Faced with a shortage of preferred prey,humpback dolphins may have broadened their dietary spectrum to maintain their daily energy intake,while their foraging group size decreased in response to the altered tradeoff between the costs and benefits of group foraging.