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

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.

The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage-A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms.

Background: The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL. Methods: Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11-35) and at the FU (t2). Results: During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2. Conclusion: Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing.

Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage-a feasibility series.

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11-35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Effects of pigment epithelium-derived factor on traumatic brain injury.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, anti-inflammatory, neurotrophic and neurogenic properties. The effect of PEDF on traumatic brain injury (TBI) has not been explored. In this study, we aimed to show the in vivo effects of PEDF on lesion volume, cell death and cell proliferation after TBI. METHODS: Rats were subjected to controlled cortical impact injury (CCII). PEDF mRNA brain levels were measured by RT-PCR. The lesion volume, cell proliferation, cell death and microglia activation were assessed in the brains of lesioned animals with intraventricular alzet infusion of PEDF or aCSF, and intraperitoneal injections of BrdU. RESULTS: We detected a significant increase of PEDF mRNA levels after TBI. PEDF intraventricular infusion showed no significant effect on the contusion volume, whereas the number of dead cells, activated microglia, BrdU-positive cells around the lesion were significantly decreased. In contrast, PEDF application increased cell proliferation in the ipsilateral subventricular zone. No effect was found on cell proliferation in the dentate gyrus. CONCLUSION: The present work indicates that PEDF acts as a multifunctional agent after TBI influencing cell death, inflammation and cell proliferation.