Fibrinogen Chains Intrinsic to the Brain

We observed fine fibrin deposition along the paravascular spaces in naive animals, which increased dramatically following subarachnoid hemorrhage (SAH). Following SAH, fibrin deposits in the areas remote from the hemorrhage. Traditionally it is thought that fibrinogen enters subarachnoid space through damaged blood brain barrier. However, deposition of fibrin remotely from hemorrhage suggests that fibrinogen chains Aα, Bβ, and γ can originate in the brain. Here we demonstrate in vivo and in vitro that astroglia and neurons are capable of expression of fibrinogen chains. SAH in mice was induced by the filament perforation of the circle of Willis. Four days after SAH animals were anesthetized, transcardially perfused and fixed. Whole brain was processed for immunofluorescent (IF) analysis of fibrin deposition on the brain surface or in brains slices processed for fibrinogen chains Aα, Bβ, γ immunohistochemical detection. Normal human astrocytes were grown media to confluency and stimulated with NOC-18 (100 μM), TNF-α (100 nM), ATP-γ-S (100 μM) for 24 h. Culture was fixed and washed/permeabilized with 0.1% Triton and processed for IF. Four days following SAH fibrinogen chains Aα IF associated with glia limitans and superficial brain layers increased 3.2 and 2.5 times (p < 0.05 and p < 0.01) on the ventral and dorsal brain surfaces respectively; fibrinogen chains Bβ increased by 3 times (p < 0.01) on the dorsal surface and fibrinogen chain γ increased by 3 times (p < 0.01) on the ventral surface compared to sham animals. Human cultured astrocytes and neurons constitutively expressed all three fibrinogen chains. Their expression changed differentially when exposed for 24 h to biologically significant stimuli: TNFα, NO or ATP. Western blot and RT-qPCR confirmed presence of the products of the appropriate molecular weight and respective mRNA. We demonstrate for the first time that mouse and human astrocytes and neurons express fibrinogen chains suggesting potential presence of endogenous to the brain fibrinogen chains differentially changing to biologically significant stimuli. SAH is followed by increased expression of fibrinogen chains associated with glia limitans remote from the hemorrhage. We conclude that brain astrocytes and neurons are capable of production of fibrinogen chains, which may be involved in various normal and pathological processes

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity

Gamma Knife stereotactic radiosurgery for intraocular retinoblastoma: a 5-year experience

External beam radiotherapy (EBR) remained for a long time the only method of treatment in children with recurrent and resistant retinoblastoma (RB). This method often leads to serious complications, including the occurrence of secondary malignant tumors. Currently, EBR is used as second-line (salvage) therapy. There is no data in the literature of using Gamma Knife stereotactic radiosurgery (GKRS) in RB treatment.Purpose. To present 5-year experience of using GKRS in patients with RB.Material and methods. 16 children (17 eyes) were treated using GKRS in the period from 2015 to 2019. Mean patient age was 34.7 months (range, 12–114 months). The eyes were classified as group B (n=4), C (n=1), D (n=12). 3 children had the last eye. All patients received systemic and local chemotherapy, all types of local treatment modalities before using GKRS. Recurrent and resistant RB was the indication for GKRS. Marginal 50% mean dose was 22 Gу (range, 20–24 Gу), depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones.Results. Complete regression was achieved in 11 patients, partial in 2. Four patients underwent enucleation after GKRS. Indications for enucleation were retinoblastoma recurrence (n=2) and vitreous hemorrhage with total retinal detachment (n=2). 13 eyes were salvaged with no signs of keratopathy, uveitis or damage of orbital and surrounding tissues during mean follow-up 30.6 months (range, 7–60 months). Сomplications of different severity occurred in 13 patients, including vitreous hemorrhage in 6 patients, which was successfully treated both conservative (n=3) and using pars plana vitrectomy with simultaneous melphalan irrigation (n=3).Conclusion. The first experience of GKRS as an alternative to enucleation in patients with RB was proved to be reasonable and successful

Neurofibromatosis: analysis of clinical cases and new diagnostic criteria

Neurofibromatoses are a group of genetic disorders with predisposing for central and peripheral nervous system tumor development. The group includes three entities: neurofibromatosis type I, neurofibromatosis type II and schwannomatosis, which are characterized by gradual phenotype development and have a partially overlapping spectrum of manifestations, which complicates diagnosis establishing, especially at the stage of clinical onset. At the same time, the emergence of new pathogenetic therapy and the high risk of transmission to descendants actualize the necessity of early diagnosis. DNA tests allow us to reliably confirm the presumed diagnosis. This article presents a review of neurofibromatoses, their clinical features and courses, modern diagnostic criteria and indications for DNA tests