Histological Examination.

<p>After follow-up angiography, histological examinations were performed. In a. a microphotograph of a representative grind-cut section from the SMA stained with van Geeson and toulene blue, is shown (scale bar = 250 µm). In b. a high power field microphotograph of van Geeson and toulene blue with phase contrast stained endothelium adjacent to a deposit tip, is shown. No cellular alterations of the composition of the blood vessel is detected (scale bar = 30 µm). In c. a microphotograph of van Geeson stained lymph node from the mesentery adjacent to a detached tip, is shown. No signs of lymph node activation is seen (scale bar = 30 µm).</p

Scanning Electron Microscopy of Detachment Zone.

<p>For the devices that failed to detach, scanning electron microscopy was performed. In this figure an overview is shown of a failed detachment with a blow up from where spectroscopic analysis indicated formation of a passive layer, possibly by Titanium – Chloride ion formation.</p

Histology of vessel perforation.

<p>Microphotograph showing the vessel perforation made by the Extroducer body with an outer diameter of 194 µm. The Extroducer makes a penetration that is on average 70 µm in diameter, indicated by arrows in this histological vessel sample stained by hematoxilin and eosin. VW indicates vessel wall and VL indicates vessel lumen, respectively. Scale bar: 20 µm.</p

<i>Ex vivo</i> and simulation data from penetration forces and blood-flow in the catheter lumen.

<p>In a. graph showing data from a loading cell connected to a longitudinally cut aorta mounted in free air with the first bar corresponding to force applied to penetrate the vessel wall from inside and out and the second bar corresponding to perforation by the depth limiting collar, an “overshooting” of the system. Error bars are Standard deviations. In b. graph showing flow rates (Y-axis) plotted against lumen radius (X-axis). The flow rate becomes small as the lumen radius is reduced. At radii over 50 micrometer, turbulent flow gives lower flow rates (open symbols) which is taken into account in the calculations with COMSOL Multiphysics as compared to a perfect laminar flow (filled symbols). In c. graph illustrating velocity fields of circular Poiseuille flows (filled symbols) and COMSOL Multiphysics (open symbols) in an Extroducer device with a 2 mm long lumen, wherein the velocity fields, driven by a pressure of 200 mmHg (Y-axis), are plotted against different lumen radius (X-axis). This shows turbulence impact in reducing the velocity in the central part of the velocity fields. At a 50 micrometer radius COMSOL Multiphysics is identical to the circular Poiseuille flow but at higher radii the impact of turbulence becomes apparent.</p

Radiological and microsurgical examples of the intervention.

<p>For full control over the procedure in the large animal trials, both a surgical microscope and high resolution angiographical series was used. In a. digital subtraction angiogram showing a detached Extroducer tip without hemorrhage, dissection or thromboembolic complications. In b. photograph showing the microsurgical view of the detached Extroducer tip. In c. x-ray image showing the detached Extroducer tip with guide catheter. In d. photograph from post-operative dissection showing the detached Extroducer tip with methylene blue injected in the surrounding tissue. In e. digital subtraction angiogram showing an extra vascular injection of 25 µl contrast agent through the Extroducer system.</p

Distribution of analysed detached tips.

<p>The distal tip placement distribution in animals not excluded, plotted against time-points for follow-up. SMA = Superior Mesenteric Artery, SCA = Subclavian artery, ECA = External Carotid Artery.</p

Follow Up of the Detached Distal Tips.

<p>In a. the initial follow up angiogram directly following detachment in the Superior Mesenteric Artery (SMA) is shown with a square marking the blow-up in b. Arrows indicate the detached distal tip. In c. an SMA angiogram, performed 80 days after the intervention in the same animal, is shown with a square indicating the blow-up in d. Arrows indicate the detached distal tip. In e. a microphotograph of a histological van Geeson and toulene blue staining prepared by grind-cutting with a detached tip <i>in situ</i>, is shown. Scale bar = 100 µm. The blow-up in f shows the parylene coating surrounding the detached tip which is marked by an arrow. Note that no fibrous response or inflammation is observable. Scale bar = 4 µm.</p

Autoradiographs following hybridisation of rat brain sections after contusion showing CD-44 and OPN – osteopontin mRNA expression

<p><b>Copyright information:</b></p><p>Taken from "Genomic responses in rat cerebral cortex after traumatic brain injury"</p><p>BMC Neuroscience 2005;6():69-69.</p><p>Published online 30 Nov 2005</p><p>PMCID:PMC1310614.</p><p>Copyright © 2005 von Gertten et al; licensee BioMed Central Ltd.</p> Note intense mRNA signal in contusion area with no visible signal in contralateral hemisphere

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

<div><p>Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury.</p></div

Regions of interest (ROIs).

<p>(A) Apparent diffusion coefficient (ADC) maps and (B) T2 weighted images with examples of ADC lesion and T2 lesion ROIs (red). (C) Cerebral blood flow (CBF) maps. (D) CBF maps with ADC overlay. ROIs used to examine the CBF of the Ischemic Core (cyan) were drawn initially in ADC maps at 60 min after reperfusion and subsequently transferred to CBF maps. ROIs delineating the Penumbra (white), regions supplied by the anterior cerebral artery (purple), and regions supplied by the posterior cerebral artery (yellow) were drawn in CBF maps.</p