Serum glial fibrillary acidic protein (GFAP)-antibody in idiopathic intracranial hypertension

Yetimler, Berrak; Tzartos, John; Şengül, Büşra; Dursun, Erdinç; Ulukan, Çağrı; Karagiorgou, Katerina; Gezen-Ak, Duygu; Sezgi̇n, Mi̇ne; Papaconstantinou, Aliki; Tzartos, Socrates J.; Orhan, Elif Kocasoy; Eki̇zoğlu, Esme; Küçükali, Cem İsmail; Baykan, Betül; Tüzün, Erdem

doi:10.1080/00207454.2020.1758084

Cited by 13 publications

(10 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some patients with this entity share similarities with IIH, such as visual impairment, papilledema, visual field defects, and intracranial hypertension (Flanagan et al, 2017 ; Chen et al, 2018 ). A subset of patients with IIH were positive toward GFAP-antibody, which might in some IIH subjects result in astrocyte dysfunction (Yetimler et al, 2021 ). Therefore, further focus on neuro-inflammation in IIH is warranted.…”

Section: Discussionmentioning

confidence: 99%

A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface

Eide

Hansson

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Idiopathic intracranial hypertension (IIH) is a neurological disease characterized by symptoms and signs of increased intracranial pressure (ICP) of unknown cause. Most attention has been given to the role of cerebrospinal fluid (CSF) disturbance and intracranial venous hypertension caused by sinus vein stenosis. We previously proposed that key pathophysiological processes take place within the brain at the glia-neuro-vascular interface. However, the relative importance of the proposed mechanisms in IIH disease remains unknown. Modern treatment regimens aim to reduce intracranial CSF and venous pressures, but a substantial proportion of patients experience lasting complaints. In 2010, the first author established a database for the prospective collection of information from individuals being assessed for IIH. The database incorporates clinical, imaging, physiological, and biological data, and information about treatment/outcome. This study retrieved information from the database, asking the following research questions: In IIH subjects responding to shunt surgery, what is the occurrence of signs of CSF disturbance, sinus vein stenosis, intracranial hypertension, and microscopic evidence of structural abnormalities at the glia-neuro-vascular interface? Secondarily, do semi-quantitative measures of abnormal ultrastructure at the glia-neurovascular differ between subjects with definite IIH and non-IIH (reference) subjects? The study included 13 patients with IIH who fulfilled the diagnostic criteria and who improved following shunt surgery, i.e., patients with definite IIH. Comparisons were done regarding magnetic resonance imaging (MRI) findings, pulsatile and static ICP scores, and immune-histochemistry microscopy. Among these 13 IIH subjects, 6/13 (46%) of patients presented with magnetic resonance imaging (MRI) signs of CSF disturbance (empty sella and/or distended perioptic subarachnoid spaces), 0/13 (0%) of patients with IIH had MRI signs of sinus vein stenosis, 13/13 (100%) of patients with IIH presented with abnormal preoperative pulsatile ICP [overnight mean ICP wave amplitude (MWA) above thresholds], 3/13 (23%) patients showed abnormal static ICP (overnight mean ICP above threshold), and 12/13 (92%) of patients with IIH showed abnormal structural changes at the glia-neuro-vascular interface. Comparisons of semi-quantitative structural variables between IIH and aged- and gender-matched reference (REF) subjects showed IIH abnormalities in glial cells, neurons, and capillaries. The present data suggest a key role of disease processes affecting the glia-neuro-vascular interface.

show abstract

Section: Discussionmentioning

confidence: 99%

A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface

Eide

Hansson

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…So far, GFAP antibody detected in serum or CSF has been reported in various disorders such as traumatic brain injury, some neoplasms, autism, Tourette syndrome, multiple sclerosis, diabetes, inflammatory brain disorders following daclizumab treatment, and idiopathic intracranial hypertension, etc. (4,(8)(9)(10)(11)(12)(13)(14). As GFAP is a cytoplasmic protein, the pathogenicity of GFAP antibody remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Perhaps it is only a biomarker for the process of immune inflammation caused by GFAP peptidespecific CD8+ T lymphocytes (2, 15). Some researchers bring forward the question whether GFAP antibody is a secondary phenomenon of reactive gliosis (13). An alternative explanation is that GFAP antibody may be accompanied by an as yet unidentified pathogenic autoantibody targeting the astrocytic plasma membrane (15).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Need for Caution in the Diagnosis of GFAP Astrocytopathy—A Case of GFAP Astrocytopathy Coexistent With Primary Central Nervous System Lymphoma

Fang

Tong

2022

Front. Neurol.

View full text Add to dashboard Cite

We reported a case of primary central nervous system lymphoma (PCNSL) coexistent with glial fibrillary acidic protein (GFAP) astrocytopathy, and discussed the problems needing attention in the diagnosis and differential diagnosis of GFAP astrocytopathy. Our patient was a 51-year-old female who presented with somnolence for a month, and memory declination for 10 days. Brain magnetic resonance imaging (MRI) demonstrated multiple abnormal enhancement lesions in bilateral basal ganglia and around the third ventricle, as well as transient T2-weighted hyper-intensity lesions at the splenium of the corpus callosum during the course of the disease. The cerebrospinal fluid (CSF) was positive for anti-GFAP antibodies by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She was initially diagnosed with autoimmune GFAP astrocytopathy. After treatment with corticosteroids for about 2 months, she displayed poor response and even worsened clinical manifestations when the dose of prednisone reduced to 45 mg. Stereotactic brain biopsy was adopted and the diagnosis of large B-cell lymphoma, non-germinal center type was established on pathological examination. The results of brain biopsy also showed perivascular inflammation and CD8+ T cell infiltration, which also accorded with GFAP astrocytopathy. After chemotherapy with rituximab and methotrexate, the patient showed clinical and radiological improvement significantly. Our findings suggest that positivity of GFAP antibody calls for cautious interpretation. Cancer screening appropriate for age, sex, and risk factors is recommended for GFAP antibody-positive patients, especially for patients with atypical clinical and radiologic manifestations.

show abstract

“…Although, the role of astrocytes is not well‐documented in response to chronic stress, it has been suggested that they may directly modify synaptic activity by the release of active molecules, called gliotransmitters (Araque et al., 2014 ). Glial fibrillary acidic protein (GFAP) is a cytoskeletal protein of astrocytes, which typically used as an important marker of astrocyte activation (Yetimler et al., 2020 ). Many studies have found that astrocytes can be activated following chronic stress (Du Preez et al., 2020 , 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress

Tofigh

Amirfakhraei

et al. 2022

Brain and Behavior

View full text Add to dashboard Cite

Background: It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)-like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD-like behavior through modulating of astrocyte activity and improvement of oxidative stress.Methods: Male NMRI mice were used to evaluate the memory function by using Morris water maze (MWM) and fear memory extinction by using freezing response. We used MK-801 (NMDAR-antagonist), L-NNA (NOS-inhibitor), NMDA (NMDAR-agonist), and L-arginine (NO-agent) to find a proper treatment. Also, immunohistochemistry, RT-PCR, and oxidative stress assays were used to evaluate the levels of astrocytes and oxidative stress. We used five mice in each experimental task. Results:Our results revealed that SIS could induce learning and memory dysfunction as well as impairment of fear memory extinction in MWM and freezing response tests, respectively. Also, we observed that combined treatment including blockage of NOS (by L-NNA, 0.5 mg/kg) and NMDAR (by MK-801, 0.001 mg/kg) at subeffective doses could result in improvement of both memory and fear memory. In addition, we observed that SIS significantly increases the GFAP expression and astrocyte activity, which results in significant imbalance in oxidative stress. Coadministration of MK-801 and L-NNA at subeffective doses not only decreases the expression of GFAP, but also regulates the oxidative stress imbalance Conclusion: Based on these results, it could be hypothesized that blockage of NO/NMDAR pathway might be a novel treatment for PTSD-like behavior in animals by inhibiting the astrocyte and regulating oxidative stress level.

show abstract

Serum glial fibrillary acidic protein (GFAP)-antibody in idiopathic intracranial hypertension

Cited by 13 publications

References 21 publications

A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface

A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface

Case Report: Need for Caution in the Diagnosis of GFAP Astrocytopathy—A Case of GFAP Astrocytopathy Coexistent With Primary Central Nervous System Lymphoma

Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress

Contact Info

Product

Resources

About