Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target.

Traumatic brain injury (TBI) is known as an acute degenerative pathology of the central nervous system, and has been shown to increase brain aquaporin 4 (AQP4) expression. Various molecular mechanisms affect AQP4 expression, including neuronal high mobility group box 1, forkhead box O3a, vascular endothelial growth factor, hypoxia-inducible factor-1 α (HIF-1 α) sirtuin 2, NF-κB, Malat1, nerve growth factor and Angiotensin II receptor type 1. In addition, inhibition of AQP4 with FK-506, MK-801 (indirectly by targeting N-methyl-D-aspartate receptor), inactivation of adenosine A2A receptor, levetiracetam, adjudin, progesterone, estrogen, V1aR inhibitor, hypertonic saline, erythropoietin, poloxamer 188, brilliant blue G, HIF-1alpha inhibitor, normobaric oxygen therapy, astaxanthin, epigallocatechin-3-gallate, sesamin, thaliporphine, magnesium, prebiotic fiber, resveratrol and omega-3, as well as AQP4 gene silencing lead to reduced edema upon TBI. This review summarizes current knowledge and evidence on the relationship between AQP4 and TBI, and the potential mechanisms involved.

A case of convexity non-aneurysmal subarachnoid hemorrhage caused by cerebral sinus thrombosis.

BACKGROUND: Convexity subarachnoid hemorrhage (cSAH) is an uncommon presentation of subarachnoid bleeding, referring to bleeding more localized to the convexities of the brain. The diagnosis of cerebral venous sinus thrombosis (CVST) can be difficult especially when patients initially present with cSAH. The authors present a case and then discuss the pathophysiology and management. CASE PRESENTATION: A 56-year-old woman with a previous history of hypertension and ischemic heart disease presented to the emergency department after experiencing it. Two seizures following a severe headache. The patient's history was negative for recent illnesses, head trauma, history of migraines, smoking, alcohol consumption, or intravenous drug use. The patient was diagnosed with CVST based on magnetic resonance venography (MRV). Genetic studies further identified homozygous mutations in the Prothrombin and MTHFR genes. Anticoagulant therapy was initiated with 60 mg of Enoxaparin twice daily and subsequently transitioned to Warfarin after 48 h continued for 3 months, and then replaced by rivaroxaban. CONCLUSIONS: This study highlights the importance of considering CVST as a cause of SAH, emphasizes the role of advanced imaging in diagnosis, and demonstrates a successful treatment approach using both traditional and direct oral anticoagulants. The insights provided in this article can contribute to improving the management of patients with CVST-related SAH.

68 Ga-DOTATATE PET/CT in the Initial Diagnosis of Patients With Clinical, Imaging, and/or Biochemical Suspicion of a Neuroendocrine Tumor.

PURPOSE: The aim of this study was to assess the yield of somatostatin receptor PET in patients with clinical, imaging, and/or biochemical suspicion of a neuroendocrine tumor (NET). PATIENTS AND METHODS: This analysis includes patients referred for the initial diagnosis of an unconfirmed NET, as part of a prospective, single-arm registry study (NCT03873870) assessing the utility of 68 Ga-DOTATATE PET/CT in the management of NETs. Inclusion criteria to this cohort consisted of elevated biomarkers and/or clinical presentation suspicious for a NET, with negative conventional cross-sectional imaging, or presence of a lesion suspicious for a NET on conventional imaging, not amenable for biopsy. Patients with histological confirmation of a NET were excluded. RESULTS: There were 220 patients included between April 2019 and March 2022 with a mean age ± SD of 59.5 ± 16.1 years with biochemical, morphological, and/or clinical suspicion of a NET. Overall, 132/220 patients (60%) had a positive 68 Ga-DOTATATE PET/CT. 68 Ga-DOTATATE PET/CT confirmed a type 2 somatostatin receptor overexpressing tumor in 123/171 (71.9%) of patients with a radiographically suspicious abnormality. The positivity rate for pancreatic, small bowel/mesenteric, adrenal, and other sites was 78/96 (81.2%), 38/57 (66.7%), 7/7 (100%), and 1/11 (9.1%), respectively. 68 Ga-DOTATATE PET/CT was positive in 9/49 (18.4%) of those with a biochemical and/or clinical suspicion of a NET. CONCLUSIONS: 68 Ga-DOTATATE PET/CT is positive in nearly 3 of 4 patients with morphological suspicion of a NET, with the highest yield in those with pancreatic and small bowel or mesenteric masses, and in approximately 1 of 6 patients with biochemical and/or clinical suspicion of a NET.

The therapeutic effects of mesenchymal stem cell (MSCs) exosomes in covid-19 disease; Focusing on dexamethasone therapy.

The study of diseases, specifically their aetiologies, their step-by-step progressions (pathogenesis), and their impact on normal structure and function, is the focus of pathology, a branch of science and medicine. In therapeutic fields, it is critical to decrease significantly elevated levels of proinflammatory cytokines. The immunomodulatory drugs such as dexamethasone have been used in several of inflammatory diseases such as Covid-19. The use of dexamethasone alone or in combination with other drugs or method such as mesenchymal stem cell (MSC) is one of the most up-to-date discussions about Covid-19. In this review, we first examined the effects of dexamethasone as monotherapy on inflammatory cytokines and then examined studies that used combination therapy of dexamethasone and other drugs such as Baricitinib, Tofacitinib and tocilizumab. Also, therapeutic aspects of MSCs are examined in this review.

The Role of Optical Coherence Tomography in Early Detection of Retinal Nerve Fiber Layer Damage in Pituitary Adenoma.

Background and objectives:This study aimed to evaluate the ability of optical coherence tomography (OCT) to differentiate eyes without obvious visual disturbances following pituitary adenomas (PAs) from normal eyes, in order to identify factors that could predict early diagnosis and timely treatment and prevent structural damage of visual pathway in patients with saddle area tumors. Material and methods:The present study was carried out between 2014-2018. Participants were divided into three groups: 23 subjects (44 eyes) in the PAs with visual field involvement (VFI) group, 10 (20 eyes) in the PAs with normal visual field (NVF) group and 22 subjects (44 eyes) in the control group. All patients received diagnostic magnetic resonance imaging (MRI), automated perimetry, visual acuity, OCT and ophthalmological assessments. Also, the degree of visual field (VF) deficit and thickness of peripapillary retinal nerve fiber layer (pRNFL) were measured by OCT and then considered for statistical analysis as predictors of early diagnostic visual involvement in the PAs. Results:All patients in the NVF and control groups (a total of 64 eyes) had normal VF. In the VFI group there were 16 eyes with complete hemianopia. Bitemporal hemianopia occurred in 20 eyes and eight eyes with concentric VF narrowing. Assessment of pRNFL thickness with OCT demonstrated the average and all quadrants of pRNFL thickness in the VFI group were significantly thinner than the pRNFL thickness in the other groups (P<0.001). The pRNFL thickness in the inferior and nasal quadrants and the average value in the NVF group were significantly thinner than the control group (P<0.05). Conclusion:If a patient has band atrophy, there is an irreversible damage and the main goal is to diagnose a nerve damage using OCT before band atrophy.

Non-coding RNAs and glioma: Focus on cancer stem cells.

Glioblastoma and gliomas can have a wide range of histopathologic subtypes. These heterogeneous histologic phenotypes originate from tumor cells with the distinct functions of tumorigenesis and self-renewal, called glioma stem cells (GSCs). GSCs are characterized based on multi-layered epigenetic mechanisms, which control the expression of many genes. This epigenetic regulatory mechanism is often based on functional non-coding RNAs (ncRNAs). ncRNAs have become increasingly important in the pathogenesis of human cancer and work as oncogenes or tumor suppressors to regulate carcinogenesis and progression. These RNAs by being involved in chromatin remodeling and modification, transcriptional regulation, and alternative splicing of pre-mRNA, as well as mRNA stability and protein translation, play a key role in tumor development and progression. Numerous studies have been performed to try to understand the dysregulation pattern of these ncRNAs in tumors and cancer stem cells (CSCs), which show robust differentiation and self-regeneration capacity. This review provides recent findings on the role of ncRNAs in glioma development and progression, particularly their effects on CSCs, thus accelerating the clinical implementation of ncRNAs as promising tumor biomarkers and therapeutic targets.