Involvement of Nrf2 in the immune regulation of Litopenaeus vannamei against Vibrio harveyi infection.

NF-E2-related factor-like-2 (Nrf2) is a transcription factor that belongs to the Cap'n'Collar transcription factor family and plays a role in regulating inflammation, autophagy, metabolism, proteostasis, and cancer prevention. However, its influence on Vibrio spp infection in L. vannamei remains uncertain. In this study, the effects of Nrf2 on the immune response in Vibrio spp infection was determined by RT-PCR and histopathological analysis. The results showed that RNAi of Nrf2 significantly decreased the expression of antioxidant-related genes (CAT, SOD and GST; p < 0.05), and significantly up-regulated inflammation-related genes (IMD, pro-PO, P38, Toll, Hsp70, NFκB and RAB6A; p < 0.05) and the apoptosis gene (caspase3). Under the infection of V. harveyi, histopathological analysis showed that after RNAi of Nrf2, the hepatopancreas of shrimp has an abnormal arrangement of hepatic tubules and vacuolization of hepatocyte; The basement membrane is peeled off and the epithelial cells are massively necrotic. Compared with the RNAi of Nrf2 group, the tissue damage in the SFN group was much lessened, and there were fewer apoptosis signals in the TUNEL assay. In conclusion, this experiment indicated that Nrf2 is involved in the regulation of inflammatory response, oxidative stress,and apoptosis induced by V. harveyi in L. vannamei.

Netrin-1 alleviates subarachnoid haemorrhage-induced brain injury via the PPARγ/NF-KB signalling pathway.

Netrin-1 (NTN-1) is a novel drug to alleviate early brain injury following subarachnoid haemorrhage (SAH). However the molecular mechanism of NTN-1-mediated protection against early brain injury following SAH remains largely elusive. This study aims to evaluate the effects and mechanisms of NTN-1 in protecting SAH-induced early brain injury. The endovascular perforation SAH model was constructed using male C57BL/6J mice, and recombinant NTN-1 was administrated intravenously. Mortality rates, SAH grade, brain water content, neurological score and neuronal apoptosis were evaluated. The expression of PPARγ, Bcl-2, Bax and nuclear factor-kappa B (NF-κB) were detected by Western blot. Small interfering RNA specific to NTN-1 receptor, UNC5B, and a selective PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), were applied in combination with NTN-1. The results suggested that NTN-1 improved the neurological deficits, reduced the brain water content and alleviated neuronal apoptosis. In addition, NTN-1 enhanced PPARγ and Bcl-2 expression and decreased the levels of Bax and NF-κB. However, the neuroprotection of NTN-1 was abolished by UNC5B and BADGE. In conclusion, our results demonstrated that NTN-1 attenuates early brain injury following SAH via the UNC5B PPARγ/NF-κB signalling pathway.

Controlled Decompression Attenuates Brain Injury in a Novel Rabbit Model of Acute Intracranial Hypertension.

BACKGROUND In the past, standard rapid decompressive craniectomy was used to alleviate the secondary damage caused by high intracranial pressure. Recent clinical studies showed that controlled decompression may have a better curative effect than rapid decompression. However, the effect on controlled decompression in animals is unclear. MATERIAL AND METHODS Totally 80 healthy male New Zealand rabbits were randomly divided into a sham group (n=20), a rapid decompression group (n=30), and a controlled decompression group (n=30). An intracranial hypertension model was induced by injecting saline into an epidural balloon catheter and reducing ICP slowly and gradually by use of a pressure pump. The model was evaluated and analyzed by general observations, imaging examination, ICP values, behavioral score, brain water content, Nissl staining, and caspase-3 protein detection. RESULTS The mortality rate was 36.7% (11/30) in the rapid group, 20% (6/30) in the controlled group, and 5% (1/20) in the sham group. The incidence of epidural hematoma in the controlled group was lower than in the rapid group (p<0.01). The ICP was significantly lower in the controlled group than in the rapid group (p<0.001), and the behavioral score in the rapid group was higher than in the controlled group (p<0.05). There was a marked difference in brain water content between the controlled group and the rapid group (p<0.01). Nissl staining demonstrated that the ratio of Nissl body in the controlled group was significantly higher than in the rapid group (p<0.01). WB detection showed the expression of Caspase-3 in the controlled group was lower than in the rapid group (p<0.05). CONCLUSIONS The results show the advantages of use of controlled decompression with intracranial hypertension. The animal model we developed provides a platform for further research on controlled decompression.