ABSTRACT
Cerebral ischemic stroke is an acute cerebrovascular disease caused by cerebral vascular occlusion, and it is associated with high incidence, disability, and mortality rates. Studies have found that excessive or insufficient autophagy can lead to cellular damage. Autophagy consists of autophagosome formation and maturation, autophagosome-lysosome fusion, degradation and clearance of autophagic substrates within autolysosomes, and these processes collectively constitute autophagic flux. Research has revealed that cerebral ischemia can induce impaired fusion between autophagosomes and lysosomes, resulting in autophagic flux impairment. Intracellular membrane fusion is mediated by three core components: N-ethylmaleimide sensitive factor (NSF) ATPase, soluble NSF attachment protein (SNAP), and soluble NSF attachment protein receptors (SNAREs). SNAREs, after mediating fusion between autophagosomes and lysosomes, remain in an inactive complex state on the autolysosomal membrane, requiring NSF reactivation into monomers to perform subsequent rounds of membrane fusion-mediated functions. NSF is the sole ATPase capable of reactivating SNAREs. Recent studies have shown that cerebral ischemia significantly inhibits NSF ATPase activity, reducing its reactivation of SNAREs. This may be a pathological mechanism for impaired fusion between autophagosomes and lysosomes, leading to neuronal autophagic flux impairment. This article discusses the pathological mechanisms of NSF ATPase inactivation, including SNAREs dysregulation, impaired fusion between autophagosomes and lysosomes, and insufficient transport of proteolytic enzymes to lysosomes, and explores approaches to improve neuronal autophagic flux through NSF ATPase reactivation. It provides references for stroke treatment improvement and points out directions for further research.
ABSTRACT
In order to explore the protective mechanism of stress-activated protein kinase JNK on neurons after ischemic stroke,the model of middle cerebral artery occlusion (MCAO) in male SD rats was established by suture methods. Anisomycin (AN), a JNK agonist, was added at the characteristic time point of autophagy, and then Western blotting and immunofluorescence were used to detect the protein expression of autophagy flow pathways in ischemic penumbra, and the effects of JNK on the stability of Bcl-2-Beclin1 complex and autophagy flow pathway were analyzed. The results showed that compared with the MCAO+Veh group, the expression levels of LC3 (
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the survival rate, complications during hospitalization, and prognostic factors in extremely preterm infants (gestational age less than 28 weeks) in the neonatal intensive care unit (NICU).</p><p><b>METHODS</b>A retrospective analysis was performed on 90 extremely preterm infants who were admitted to the NICU between January 2011 and March 2013 to investigate the perinatal data, delivery and resuscitation, ventilation/oxygen supply during hospitalization, mortality, and the incidence of severe (grade III/IV) intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), and septicemia.</p><p><b>RESULTS</b>Among the 90 extremely preterm infants, the gestational age, birth weight, overall survival rate, mortality, and withdrawal rate were 26±1 weeks, 898±165 g, 57%, 9%, and 34%, respectively. The incidence rates of neonatal respiratory distress syndrome, BPD, PDA, ROP, and grade III/IV IVH were 88%, 85%, 69%, 68%, and 31%, respectively. The surviving infants had a mean length of hospital stay of 83±18 days and a mean weight at discharge of 2 419±300 g. The multivariate logistic regression analysis showed that grade III/IV IVH and pulmonary hemorrhage were high-risk factors for death or withdrawal, while antenatal corticosteroids were the protective factor for outcome (P<0.05).</p><p><b>CONCLUSIONS</b>The survival rate of extremely preterm infants is still much lower than that in developed countries. grade III/IV IVH, and pulmonary hemorrhage are important prognostic factors.</p>