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Albumin storage in neoplastic astroglial elements of gangliogliomas.

ABSTRACT: Low-grade neuroepithelial tumors are frequent neuropathological findings in patients with pharmacoresistant epilepsies. Little is known regarding epileptogenic mechanisms in this group of neoplasms with gangliogliomas (GG) as the most common entity. Presence of hemosiderin deposits in GG points to impairment of the blood-brain barrier (BBB). Therefore, we hypothesized a potential role of BBB dysfunction and astrocytic albumin uptake as potential epileptogenic factor in GG.Prussian blue staining and fluorescent double-immunohistochemistry with antibodies against albumin, GFAP, CD34 and GLUT-1 were used to analyze hemosiderin deposits and astroglial albumin accumulation in tumor and adjacent pre-existing brain tissue of GG (n=10) and several control groups, i.e. dysembryoplastic neuroepithelial tumors (DNT; n=5), focal cortical dysplasia with balloon cells (FCD IIb; n=10), astrocytomas WHO grade II (n=5) and clear renal cell carcinoma brain metastases (RCCM, n=6).Our results revealed strong hemosiderin deposits in GG. Intriguingly, we noted substantial albumin uptake exclusively in neoplastic glial cell components of GG and DNT, whereas no significant albumin was present in perilesional reactive astrocytes. Strikingly, we did not observe substantial albumin uptake in further controls.Glial albumin uptake was restricted to long-term epilepsy associated, vasculature-containing tumors. Intratumoural BBB dysfunction in concert with subsequent accumulation of albumin by neoplastic glial cell elements represent a new putatively epileptogenic mechanism for long-term epilepsy-associated tumors.

SUBMITTER: Schmitz AK

PROVIDER: S-EPMC3646260 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Albumin storage in neoplastic astroglial elements of gangliogliomas.

Schmitz Ann Kristin AK Grote Alexander A Raabe Anna A Urbach Horst H Friedman Alon A von Lehe Marec M Becker Albert J AJ Niehusmann Pitt P

Seizure 20121120 2

<h4>Purpose</h4>Low-grade neuroepithelial tumors are frequent neuropathological findings in patients with pharmacoresistant epilepsies. Little is known regarding epileptogenic mechanisms in this group of neoplasms with gangliogliomas (GG) as the most common entity. Presence of hemosiderin deposits in GG points to impairment of the blood-brain barrier (BBB). Therefore, we hypothesized a potential role of BBB dysfunction and astrocytic albumin uptake as potential epileptogenic factor in GG.<h4>Met ...[more]

PMID: 23182422

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Project description:PurposeIntracerebral vascular malformations including cavernous angiomas (CAs) and arteriovenous malformations (AVMs) are an important cause of chronic pharmacoresistant epilepsies. Little is known about the pathogenetic basis of epilepsy in patients with vascular malformations. Intracerebral deposits of iron-containing blood products have been generally regarded as responsible for the strong epileptogenic potential of CAs. Here, we have analyzed whether blood-brain barrier (BBB) dysfunction and subsequent astrocytic albumin uptake, recently described as critical trigger of focal epilepsy, represent pathogenetic factors in vascular lesion-associated epileptogenesis.MethodsWe examined the correlation between hemosiderin deposits, albumin accumulation, and several clinical characteristics in a series of 80 drug-refractory epilepsy patients with CAs or AVMs who underwent surgical resection. Analysis of clinical parameters included gender, age of seizure onset, epilepsy frequency, duration of epilepsy before surgery, and postoperative seizure outcome classification according to Engel class scale. Hemosiderin deposits in the adjacent brain tissue of the vascular lesion were semiquantitatively analyzed. Fluorescent double-immunohistochemistry using GFAP/albumin costaining was performed to study albumin extravasation.Key findingsOur results suggest that a shorter duration of preoperative epilepsy is correlated with significantly better postsurgical outcome (p < 0.05), whereas no additional clinical or neuropathologic parameter correlated significantly with the postsurgical seizure situation. Intriguingly, we observed strong albumin immunoreactivity within the vascular lesion and in perilesional astrocytes (57.65 ± 4.05%), but not in different control groups.SignificanceOur present data on albumin uptake in brain tissue adjacent to AVMs and CAs suggests BBB dysfunction and accumulation of albumin within astrocytes as a new pathologic feature potentially associated with the epileptogenic mechanism for vascular lesions and provides novel therapy perspectives for antiepileptogenesis in affected patients.

Project description:(1) Background: Gangliogliomas comprise a small number of brain tumors. They usually present as World Health Organization (WHO) grade I, and they delineate on gadolinium-enhanced MRI; the surgical goal is wide radical resection, and the course thereafter is usually benign. Fluorescein sodium (FL) tends to accumulate in areas with altered blood-brain barrier (BBB). Thus far, the results provided by prospective and retrospective studies show that the utilization of this fluorophore may be associated with better visualization and improvement of resection for several tumors of the central nervous system. In this study, we retrospectively studied the effect of fluorescein sodium on visualization and resection of gangliogliomas. (2) Methods: Surgical databases in three neurosurgical departments (Regensburg University Hospital; Besta Institute, Milano, Italy; and Liv Hospital, Istanbul, Turkey), with approval by the local ethics committee, were retrospectively reviewed to find gangliogliomas surgically removed by a fluorescein-guided technique by the aid of a dedicated filter on the surgical microscope from April 2014 to February 2020. Eighteen patients (13 women, 5 men; mean age 22.9 years, range 3 to 78 years) underwent surgical treatment for gangliogliomas during 19 operations. Fluorescein was intravenously injected (5 mg/kg) after general anesthesia induction. Tumors were removed using a microsurgical technique with the YELLOW 560 Filter (YE560) (KINEVO/PENTERO 900, Carl Zeiss Meditec, Oberkochen, Germany). (3) Results: No side effects related to fluorescein occurred. In all tumors, contrast enhancement on preoperative MRI correlated with bright yellow fluorescence during the surgical procedure (17 gangliogliomas WHO grade I, 1 ganglioglioma WHO grade II). Fluorescein was considered helpful by the operating surgeon in distinguishing tumors from viable tissue in all cases (100%). Biopsy was intended in two operations, and subtotal resection was intended in one operation. In all other operations considered preoperatively eligible, gross total resection (GTR) was achieved in 12 out of 16 (75%) instances. (4) Conclusions: The use of FL and YE560 is a readily available method for safe fluorescence-guided tumor resection, possibly visualizing tumor margins intraoperatively similar to contrast enhancement in T1-weighted MRI. Our data suggested a positive effect of fluorescein-guided surgery on intraoperative visualization and extent of resection during resection of gangliogliomas.

Project description:S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC-electrospray ionization-MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at -80 °C, -20 °C, and room temperature and exposed to multiple freeze-thaw cycles and other adverse conditions in order to assess the possibility that protein oxidation may occur as a result of poor sample storage or handling. Samples from a healthy donor and a participant with poorly controlled type 2 diabetes started at the same low level of protein oxidation and behaved similarly; significant increases in albumin oxidation via S-cysteinylation were found to occur within hours at room temperature and days at -20 °C. Methionine oxidation of apoA-I took place on a longer time scale, setting in after albumin oxidation reached a plateau. Freeze-thaw cycles had a minimal effect on protein oxidation. In matched collections, protein oxidation in serum was the same as that in plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the degree to which vials were sealed. ApoA-I, however, was unexpectedly found to oxidize faster in samples with lower surface-area-to-volume ratios. An initial survey of samples from patients with inflammatory conditions normally associated with elevated oxidative stress-including acute myocardial infarction and prostate cancer-demonstrated a lack of detectable apoA-I oxidation. Albumin S-cysteinylation in these samples was consistent with known but relatively brief exposures to temperatures above -30 °C (the freezing point of blood plasma). Given their properties and ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma specimen integrity based on direct measurement of oxidative molecular damage that can occur under suboptimal storage conditions.

Project description:Background and objectivesBecause there is substantial biologic intraindividual variation in albumin excretion, randomized trials of albuminuria-reducing therapies may need multiple urine samples to estimate daily urinary albumin excretion. Mailing spot urine samples could offer a convenient and cost-effective method to collect multiple samples, but urine albumin-to-creatinine ratio stability in samples stored at ambient temperatures for several days is unknown.Design, setting, participants, & measurementsPatients with kidney disease provided fresh urine samples in two tubes (with and without boric acid preservative). Reference aliquots from each participant were analyzed immediately, whereas remaining aliquots were subject to different handling/storage conditions before analysis, including delayed processing for up to 7 days at three different storage temperatures (4°C, 18°C, and 30°C), multiple freeze-thaw cycles, and long-term frozen storage at -80°C, -40°C, and -20°C. We calculated the mean percentage change in urine albumin-to-creatinine ratio for each condition, and we considered samples stable if the 95% confidence interval was within a ±5% threshold.ResultsNinety-three patients provided samples with detectable albuminuria in the reference aliquot. Median (interquartile range) urine albumin-to-creatinine ratio was 87 (20-499) mg/g. The inclusion of preservative had minimal effect on fresh urine albumin-to-creatinine ratio measurements but reduced the changes in albumin and creatinine in samples subject to processing delay and storage conditions. The urine albumin-to-creatinine ratio was stable for 7 days in samples containing preservative at 4°C and 18°C and 2 days when stored at 30°C. It was also stable in samples with preservative after three freeze-thaw cycles and in frozen storage for 6 months at -80°C or -40°C but not at -20°C.ConclusionsMailed urine samples collected with preservative and received within 7 days if ambient temperature is ≤18°C, or within 2 days if the temperature is higher but does not exceed 30°C, are suitable for the measurement of urine albumin-to-creatinine ratio in randomized trials. Preserved samples frozen to -40°C or -80°C for 6 months before analysis also seem suitable.

Dataset Information

Albumin storage in neoplastic astroglial elements of gangliogliomas.

Publications

Albumin storage in neoplastic astroglial elements of gangliogliomas.

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