The immune-inflammatory responses on the hypothalamic-pituitary-adrenal axis and the neurovascular unit in perioperative neurocognitive disorder.

Perioperative neurocognitive disorders (PNDs) refer to a wide spectrum of cognitive impairment persisting days to even after a year postoperative with significant morbidity and mortality. However, despite much efforts involving perioperative managements, PNDs are still prevalent with no standard preventative and therapeutic strategy. To overcome PNDs, a better understanding of pathophysiology of PNDs is crucial and a large number of studies have proven that immune-inflammatory responses from surgical stress are involved in the abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis and destabilization of neurovascular unit (NVU) that lead to PNDs. The HPA axis is one of the key components to maintaining physiological homeostasis in response to stress. Under normal conditions, the HPA axis is involved in multiple roles from memory consolidation to regulating the circadian rhythm by activating adrenal cortex to secret cortisol. However, when overwhelmed with inflammatory response from surgical stress, HPA axis may be abnormally activated to release excessive glucocorticoids to cause PNDs. In addition, NVU, the functional unit of the brain essential for maintaining blood brain barrier and cerebral blood flow, is another possible factor that may lead to PNDs as compromised NVU from inflammatory response can result in disrupted blood brain barrier and impaired brain homeostasis. Therefore, the interaction of immune-inflammatory response with the HPA axis and the NVU seems to play a significant role and therapeutic and/or preventive strategies focused on these interactions may be promising direction for future managements of PNDs.