TSPO exacerbates acute cerebral ischemia/reperfusion injury by inducing autophagy dysfunction.

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.

Endovascular recanalization for symptomatic chronic internal carotid artery occlusion: a study of 19 cases / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of endovascular recanalization in the treatment of chronically occluded internal carotid artery (COICA).Methods:From January 2014 to January 2019, patients over 50 years of age with symptomatic COICA underwent endovascular recanalization in the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University were enrolled retrospectively. The modified Rankin Scale (mRS) was used to evaluate the improvement of neurological function.Results:A total of 19 patients with symptomatic COICA were enrolled, of which 16 (84.21%) were successfully recanalized. None of the patients had severe neurological deficits during the periprocedural period and after procedure. The neurological function of patients with successful recanalization gradually improved over time. The neurological function improved in 4 patients (25.0%) at 24 h after endovascular treatment and 9 (56.3%) at 18 months postprocedural follow-up. The follow-up of CT angiography showed that the internal carotid artery in patients with successful recanalization was unobstructed, and there was no obvious in-stent stenosis.Conclusion:Endovascular recanalization is feasible, safe and effective in patients with symptomatic COICA.