BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Melatonin alleviates early brain injury by inhibiting the NRF2-mediated ferroptosis pathway after subarachnoid hemorrhage.

Ferroptosis is a novel form of cell death that plays a critical role in the pathological and physiological processes of early brain injury following subarachnoid hemorrhage. Melatonin, as the most potent endogenous antioxidant, has shown strong protective effects against pathological changes following subarachnoid hemorrhage, but its impact on ferroptosis induced by subarachnoid hemorrhage remains unexplored. In our study, we established a subarachnoid hemorrhage model in male SD rats. We found that subarachnoid hemorrhage induced changes in ferroptosis-related indicators such as lipid peroxidation and iron metabolism, while intraperitoneal injection of melatonin (40 mg/kg) effectively ameliorated these changes to a certain degree. Moreover, in a subset of rats with subarachnoid hemorrhage who received pre-treatment via intravenous injection of the melatonin receptor antagonist Luzindole (1 mg/kg) and 4P-PDOT (1 mg/kg), we found that the protective effect of melatonin against subarachnoid hemorrhage includes inhibition of lipid peroxidation and reduction of iron accumulation depended on melatonin receptor 1B (MT2). Furthermore, our study demonstrated that melatonin inhibited neuronal ferroptosis by activating the NRF2 signaling pathway, as evidenced by in vivo inhibition of NRF2. In summary, melatonin acts through MT2 and activates NRF2 and downstream genes such as HO-1/NQO1 to inhibit ferroptosis in subarachnoid hemorrhage-induced neuronal injury, thereby improving neurological function in rats. These results suggest that melatonin is a promising therapeutic target for subarachnoid hemorrhage.

Application of free flap pedicled with supracarpal cutaneous branch of ulnar artery in repairing of finger replantation / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate clinical application and clinical outcomes of free flap pedicled with supracarpal cutaneous branch of ulnar artery in repairing of finger replantation with skin defect.</p><p><b>METHODS</b>From April 2007 to March 2013,25 patients affected by finger amputation with skin defect were replanted and repaired by free flap pedicled with supracarpal cutaneous branch of ulnar artery. Among them, 18 patients were male and 7 were female,with an average age of 31.5 years old (ranged 16 to 58). The time of trauma to admission ranged from 45 to 210 min (averaged 105). Fifteen patients were complete separted, and 10 patients were non-complete separated. The area of flaps ranged from 3.5 cm x 2.0 cm to 4.5 cm x 3.0 cm, and the vessels were anastomosed through end-to-end. The functional evaluation standard of finger replantation was used to evaluate the postoperative function.</p><p><b>RESULTS</b>Twenty-four cases were finally survived. Two flaps occurred vascular crisisin within 48 h after operation, one of which was survived after anti-vasospasm treatment and changing dressing,another was replanted finger for failed to survive. One had infection and healed after changing dressing. Twenty-four cases were followed up from 3 to 38 months with an average of 16.5 months. The appearance and texture of flaps were satisfactory, and the superficial senses of pain and touch were recovered,and two-point discrimination was 5.5 to 11 mm (averaged 7.4 mm). According to functional evaluation standard finger replantationissued by Hand Surgery Association of Chinese Medical Association, 8 cases got excellent results, 14 good and 2 poor.</p><p><b>CONCLUSION</b>The free flap pedicled with supracarpal cutaneous branch of ulnar artery can be used in complex finger replantation with skin and vessels defect, which can extend operation indications, recover function and appearance for maximum.</p>