The change of plasma pituitary adenylate cyclase-activating polypeptide levels after aneurysmal subarachnoid hemorrhage

Abstract

Objective -Elevated circulating pituitary adenylate cyclase-activating polypeptide (PACAP) levels have been demonstrated to be associated with clinical outcomes of severe traumatic brain injury. The current study aimed to confirm whether elevated plasma PACAP levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). Materials and methods -One hundred and eighteen aSAH patients and 118 controls were recruited. Plasma PACAP concentrations were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6 months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Results -The admission PACAP levels were significantly elevated in all patients (296.6 AE 119.7 pg/ml) compared with controls (77.1 AE 17.9 pg/ml, P < 0.001). Plasma PACAP levels were independently associated with clinical severity indicated by World Federation of Neurological Surgeons (WFNS) score (t = 4.745, P < 0.001) and Fisher score (t = 4.239, P < 0.001) using a multivariate linear regression. PACAP was identified as an independent predictor for 6-month mortality [odds ratio (OR), 1.014; 95% confidence interval (CI), 1.005-1.030; P < 0.001] and 6-month unfavorable outcome (OR, 1.012; 95% CI, 1.006-1.028; P < 0.001) and 6-month overall survival (hazard ratio, 1.016; 95% CI, 1.008-1.023; P < 0.001) using a binary logistic regression analysis and a Cox's proportional hazard analysis, respectively. PACAP had similar predictive values compared with WFNS score and Fisher score according to the receiver operating characteristic curve analysis. Conclusions -Higher plasma PACAP levels are associated with clinical severity and long-term prognosis of aSAH patients, and PACAP has potential to be a good prognostic biomarker of aSAH.

Serum mannose-binding lectin levels after aneurysmal subarachnoid hemorrhage

“…In addition, the mean age of aSAH patients in this study was about 15 years younger than that of most cases (35). Nevertheless, in eastern part of China, the mean age of aSAH patients reported in some articles (36)(37)(38) was similar to that in our study. This diversity in age may be derived from the differences of races and regions.…”

PACAP as a Potential Biomarker: Alterations of PACAP Levels in Human Physiological and Pathological Conditions

“…The authors suggested that PACAP could be a good prognostic predictor in hemorrhage patients and hypothesized that the elevated blood PACAP levels may refl ect an overproduction of PACAP as a pathological response to the loss of neural tissue in the CNS and it might be associated with the neuroprotective effects of the neuropeptide. Another recent study has confi rmed these fi ndings in aneurysmal subarachnoid hemorrhage [ 15 ]. These authors examined 118 hemorrhage patients and compared them to 118 controls.…”

“…Hemorrhage patients had significantly elevated PACAP levels on admission and plasma PACAP levels were independently associated with clinical severity scores. The neuropeptide was identifi ed as an independent predictor of survival [ 15 ], suggesting that PACAP might be a potential prognostic biomarker of subarachnoid hemorrhage.…”

The Neuroprotective and Biomarker Potential of PACAP in Human Traumatic Brain Injury

“…Changes in serum PACAP levels have been described in nephrotic syndrome and in cardiomyopathies, where a decrease has been detected [48,49]. Regarding nervous system conditions, elevation has been found in acute aneurysmal subarachnoid hemorrhage [50], in acute spontaneous basal ganglia hemorrhage [51], in ictal phases of migraine [52][53][54], while decreases have been described in interictal phases of migraine [52,55] and in female post-traumatic stress syndrome patients [56]. CSF PACAP levels are decreased in Alzheimer's disease [39,40] and multiple sclerosis [57].…”