alpha-synuclein and Postoperative-Complications

Stress-induced α-synuclein aggregation, especially the most toxic species (oligomers), may precede synaptic and cognitive dysfunction. Under pathological conditions, α-synuclein is degraded primarily through the autophagic/lysosomal pathway. We assessed the involvement of autophagy in α-synuclein aggregation and cognitive impairment following general anesthesia and surgical stress. Autophagy was found to be suppressed in the aged rat hippocampus after either 4-h propofol anesthesia alone or 2-h propofol anesthesia during a laparotomy surgery. This inhibition of autophagy was accompanied by profound α-synuclein oligomer aggregation and neurotransmitter imbalances in the hippocampus, along with hippocampus-dependent cognitive deficits. These events were not observed 18 weeks after propofol exposure with or without surgical stress. The pharmacological induction of autophagy using rapamycin markedly suppressed α-synuclein oligomerization, restored neurotransmitter equilibrium, and improved cognitive behavior after prolonged anesthesia or anesthesia combined with surgery. Thus, both prolonged propofol anesthesia alone and propofol anesthesia during surgery impaired autophagy, which may have induced abnormal hippocampal α-synuclein aggregation and neurobehavioral deficits in aged rats. These findings suggest that the activation of autophagy and the clearance of pathological α-synuclein oligomers may be novel strategies to ameliorate the common occurrence of postoperative cognitive dysfunction.

Topics: alpha-Synuclein; Anesthesia; Animals; Autophagy; Cognition Disorders; Disease Models, Animal; Hippocampus; Male; Neurons; Postoperative Complications; Rats; Surgical Procedures, Operative

The clinical characteristics of postoperative delirium are similar to core features of α-synuclein-related cognitive disorders, such as dementia with Lewy bodies or Parkinson disease dementia. We therefore investigated the α-synuclein pathology in patients who experienced postoperative delirium after gastrectomy for stomach cancer.. Patients with and without postoperative delirium were selected among patients undergoing total gastrectomy for primary gastric cancer from 2007 to 2011 (each n = 16) at the university hospital. Immunohistochemical staining for α-synuclein of both normal and phosphorylated form was performed in the myenteric plexus. A logistic regression analysis was applied to identify independent predictors of postoperative delirium.. No significant differences were observed for age, sex, operation time, or onset of delirium after total gastrectomy between patients with and without postoperative delirium. Patients with postoperative delirium had a higher frequency of intensive care unit admissions (43.8 vs 6.3%, p = 0.037) and α-synuclein-positive pathologies of normal (56.3 vs 12.5%, p = 0.023) and phosphorylated form (43.8 vs 6.3%, p = 0.037) compared with those without postoperative delirium. A logistic regression analysis revealed that immunoreactivity for normal α-synuclein (odds ratio [OR] 9.20) and intensive care unit admission (OR 11.97) were independently associated with postoperative delirium.. These results suggest that underlying α-synuclein pathologies in the stomach are associated with postoperative delirium, implying that postoperative delirium represents a preclinical stage of α-synuclein related to cognitive disorders.

Topics: Aged; alpha-Synuclein; Delirium; Female; Gastrectomy; Humans; Male; Myenteric Plexus; Postoperative Complications; Postoperative Period; Regression Analysis; Stomach Neoplasms