Both coiling and clipping induce the time-dependent release of endogenous neuropeptide Y into serum

Abstract

Background: The vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY.

Methods: 58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t₀), (2) periprocedurally (t₁), (3) 6 h postprocedurally (t₂), (4) 72 h postprocedurally (t₃), and (5) at the 6-week follow-up (FU; t₄) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA.

Results: Except for time point t₀, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t₃, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t₁, t₃, and t₄, reaching a climax at FU (0.551 ± 0.304 ng/mL).

Conclusion: Our study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients.

Keywords: biomarker; cerebrovascular manipulation; clip; cognition; coil; neuropeptide Y (NPY); outcome; unruptured intracranial aneurysms (UIA).

Figure 1

Flowchart. Study design, selection criteria, and reasons for exclusion of potentially eligible cases.

Figure 2

Temporal dynamics of endogenous neuropeptide Y (NPY) levels in serum, plotted against the different types of manipulation on the central and peripheral nervous system. The line graph with error indicators displays the treatment-dependent dynamics of mean values of NPY in serum over time (t₀: before treatment, t₁: periprocedurally, t₂: 6 h postprocedurally, t₃: 72 h postprocedurally, and t₄: at the 6-week follow-up (FU) in (A) the vascular versus the non-vascular group, and in (B) all four subgroups: (A): The black line chart with circles represents the vascular group, the squares the non-vascular group. The vascular group showed significantly higher NPY values compared to the non-vascular group in all time points except t₀ (p < 0.05). (B): Intragroup comparison of endovascular aneurysm occlusion (EV) subgroup (triangle down), microsurgical clipping (MS) subgroup (diamond), convexity meningioma (CM) subgroup (stars), and degenerative lumbar spine disease (LD) subgroup (triangle up). The asterisks indicate p-values smaller than 0.05, resulting from the repeated measure ANOVA, comparing t₁-t₄ against t₀ as control. The MS subgroup displays significantly increased values on t₁, but levels down to values not significantly different compared to t₀. In contrast, the EV subgroup also increases significantly on t₁, but stays higher throughout the entire observation period. Neither the CM nor the LD subgroup showed any significant change compared to t₀. Each symbol displays the mean level of serum NPY in [ng/ml] for each (sub-)group, indicating significantly higher mean NPY concentrations in the vascular group from t₁ onward. At t₃, the EV subgroup showed significantly higher NPY levels than the MS subgroup (p = 0.021). Statistical significance: *p < 0.05.