Neuroregenerative activity of the dipeptide mimetic of Brain Derived Neurotrophic Factor GSB-106 under experimental ischemic stroke

Background: A dimeric dipeptide mimetic of the BDNF loop 4, bis(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106), which activates TrkB, PI3K/AKT, MAPK/ERK and PLC-γ1 was created at the V.V. Zakusov Research Institute of Pharmacology. GSB-106 showed neuroprotective activity in vitro and in vivo at systemic administration. Objective: In this work, we studied the GSB-106 effect on the cerebral infarct volume, as well as on neurogenesis and synaptogenesis under experimental ischemic stroke, induced by intravascular occlusion of the middle cerebral artery in rats. Methods: GSB-106 was administered i.p. in a dose of 0.1 mg/kg 24 h after surgery and then once a day, with the end of administration on the day 6 after surgery. On the day 7 brain samples were collected for morphometric and biochemical (Western-blot) analysis. Results: It was established that GSB-106 reduced the brain damage volume by 24%, restores impaired neurogenesis and/or gliogenesis (by Ki-67) in the hippocampus and in the striatum and completely restored the reduced immunoreactivity to synaptic markers synaptophysin and PSD-95 in the striatum. Conclusions: Thus, the dimer dipeptide BDNF mimetic GSB-106 exhibits neuroregenerative properties at clinically relevant time window (24 h) in a model of ischemic stroke presumably due to stimulation of neurogenesis (and/or gliogenesis) and synaptogenesis.

Diagnostic and Interventional Optical Angioscopy in Ex Vivo Carotid Arteries

BACKGROUND: Angioscopy – or endovascular endoscopy – is a catheter-based technique employing a flexible fiberoptic angioscope to directly visualize arterial lumen. Poor resolution and excessive stiffness of pre-existent angioscopes limited their use clinically. Recent advances resulted in novel fused optical fiber bundle angioscopes with improved flexibility and imaging resolution. Use of these devices in endovascular neurosurgery is still largely unexplored. OBJECTIVE: To evaluate image quality and feasibility of optical angioscopes for diagnostic and interventional neuro-angioscopy in carotid arteries of human cadavers. METHODS: A 5-F optical angioscope was used in human cadaveric carotid arteries to inspect integrity of arterial walls, identify atherosclerotic plaques and associated lesions prone to thrombogenicity, place intravascular occlusion coils, and deploy endovascular stents with real-time visualization. RESULTS: Angioscopy provided key information about endoluminal anatomy such as presence and characteristics of atherosclerotic plaques and thrombogenic lesions not detected by conventional diagnostic methods. Direct real-time visualization of vascular lumen during endovascular interventions provided information on spatial distribution of coils, coil loop herniation, and apposition of stent cells against carotid artery wall complementary to angiography. CONCLUSIONS: Fused optical fiber bundle angioscopes provide good-quality endoluminal images in human carotid arteries. Their use can feasibly assist in navigation of extracranial carotid arteries to inspect integrity of the arterial wall and identify atherosclerotic plaques and associated lesions vulnerable to thrombogenicity, allow placement of intravascular occlusion coils, and assess apposition of stents to vessel wall. Further in Vivo validation needs to be conducted along with additional research to improve image quality, flexibility, and size of angioscopes.

A new method for superselective middle cerebral artery infusion in the rat

Object Selective intraarterial drug delivery is used to achieve enhanced local uptake with reduced systemic side effects. In the present paper the authors describe and characterize a new microcatheter-based model of superselective perfusion of the middle cerebral artery (MCA) in rats combined with blockade of blood flow through the MCA. Methods Selectivity of administration was shown by infusion of Evans blue which diffusely stained the MCA territory, indicating an increased permeability of the blood–brain barrier during the blockade of blood flow to the MCA. Perfusion of autologous blood through the microcatheter resulted in a flow rate–related increase in the cerebral blood flow measured by laser Doppler flowmetry. Similarly, infusion of an artificial O2 carrier, Oxycyte, was accompanied by an increase in tissue oxygenation as measured using a Licox sensor. Blockade of blood flow to the MCA with the new microcatheter for an extended period of time resulted in the development of ischemia, which was comparable to that induced by intravascular occlusion using a silicone-coated thread. In a 24-hour MCA occlusion model, selective administration of a low dose of MK-801 (0.3 mg/kg body weight) resulted in a significantly smaller infarct volume than systemic application (339 ± 53 mm3 compared with 508 ± 26 mm3, p < 0.001). Conclusions This new model of superselective MCA infusion is a valuable tool for investigating the effect of selective delivery and enhanced drug uptake into cerebral ischemic tissue. Without constant blockade of blood flow through the MCA it may also be useful for enhanced drug uptake, gene transfer, or application of stem cells in other neuro-pathological conditions.

The evaluation of uterine arteries embolization value in functional surgery in patients with uterine myoma

The experience of constant embolization of uterine arteries (60 patients) has shown that constant intravascular occlusion of uterine arteries in some cases may be considered as rational intervention and an alternative for organ-saved surgery. Temporary embolization of uterine arteries (20 patients) orientated to decreasing of intraoperative bleeding risk allows to perform reconstructive-plastic uterine surgery in optimal condititons.

Preliminary report of a hollow-centered balloon for intravascular occlusion of intracranial aneurysms or arteriovenous fistulas

✓ A doughnut-shaped balloon has been designed that can be inserted intravascularly by catheter to occlude the orifice of an intracranial berry or giant aneurysm or arteriovenous fistula. The blood in the parent artery can continue to flow uninterrupted through the hole in the balloon. In a preliminary study, an arteriovenous fistula was successfully obliterated in a dog. The technique for placing the balloon is described.