Mechanistic Study of PK2 Pathway in Alleviating Perioperative Neurocognitive Disorders by Improving Neurometabolic Uncoupling

Starting soon

Conditions studied: Perioperative Neurocognitive Disorders

In brief

The term perioperative neurocognitive disorders (PND) is derived from postoperative cognitive dysfunction (POCD), and has been renamed as PND in recent years in accordance with the latest international consensus. PND specifically refers to changes in mental, social and cognitive abilities in patients following surgery; in severe cases, personality changes and reduced social functioning may also occur. As a serious complication affecting the central nervous system (CNS), apart from surgical trauma, advanced age is widely recognized as a critical factor contributing to the development and progression of PND. Its adverse effects represent a major challenge for the rapidly growing elderly population worldwide. It is currently believed that the decline in cognitive functions such as memory and attention observed in some patients after surgery may be associated with inflammatory responses in the brain. Surgical stress may activate supporting cells in the brain, such as astrocytes. When these cells are abnormally activated, they may fail to maintain normal neuronal function, thereby disrupting brain homeostasis and leading to cognitive impairment. Recent studies have shown that these glial cells exert distinct effects on neurons under different phenotypes: some phenotypes promote neural repair and protection, whereas others exacerbate neural injury. Evidence suggests that in multiple neurological disorders, the pro-inflammatory phenotype of glial cells is closely associated with cognitive impairment. Prokineticin-2 (PK2) is an endogenous signaling molecule involved in the regulation of diverse physiological processes, including inflammatory responses, energy metabolism, and neuroprotection. Previous studies have demonstrated that PK2 exerts protective effects in various neurological disease models, improving neuronal function and alleviating cognitive or motor deficits. Our preliminary animal experiments revealed reduced brain PK2 levels, especially in memory-related regions, in mice with postoperative cognitive dysfunction. Exogenous supplementation of PK2 significantly restored brain cell function and improved cognitive performance in these mice, suggesting that PK2 may play an important role in maintaining cerebral function after surgery. However, it remains unclear whether changes in PK2 levels in clinical patients correlate with the occurrence and severity of postoperative cognitive dysfunction. This study aims to investigate changes in circulating PK2 levels and explore their association with postoperative cognitive alterations, so as to provide evidence for the improved prevention and identification of PND. We plan to enroll elderly patients undergoing hip replacement surgery at Nanjing First Hospital. By analyzing PK2 expression levels and dynamic changes, combined with postoperative neuropsychological scale assessments, we will evaluate the correlation between serum PK2 levels and the clinical incidence of PND, and further verify the intrinsic link between PK2 levels and the pathogenesis of PND.

Key facts

Study ID
NCT07652008
Run by
Nanjing First Hospital, Nanjing Medical University
People needed
40
Starts
2026-06-01
Expected to finish
2027-03-31
Last updated by the study team
2026-06-16

Who can join

Age: 65 and older, up to 80. Sex: any. Healthy volunteers: accepted.

You may qualify if…

You may not qualify if…

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.