Brain Hemorrhages (Mar 2023)
Delayed cerebral ischemia associated with surgery for pituitary macroadenomas that express elevated levels of PACAP
Abstract
Delayed cerebral ischemia (DCI) and cerebral vasospasm (VS) are rare but serious post-operative complications after surgery for pituitary macroadenomas; the mechanism of which are poorly understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a vasoactive neuropeptide expressed in pituitary adenomas and may play a role in DCI/VS. The aim of this case-control study was to investigate the association between tumor expression of PACAP and DCI/VS following pituitary surgery. Tumor tissue from five patients with DCI/VS following pituitary surgery and nine matched controls were evaluated for PACAP expression by immunohistochemistry. Nuclear PACAP expression was significantly elevated in patients with DCI/VS following pituitary surgery compared to controls (0.396 ± 0.0.16 a.u. vs 0.093 ± 0.04 a.u, p < 0.0001). There was a positive linear relationship between nuclear PACAP expression and pre-operative tumor volume (r2 = 0.41, p < 0.02) with a significant difference in slopes between the DCI/VS group compared to controls (y = x(5.0 × 10−3), r2 = 0.76 vs y = x(7.4 × 10−4), r2 = 0.07, p < 0.05). Elevated levels of tumor PACAP expression is associated with DCI/VS following pituitary surgery and may have a role in tumor growth. PACAP signaling may play a role the development of DCI, but further studies are needed.