Browsing by Author "Tuor, Ursula I."
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Item Open Access Development of a Model of Recurrent Stroke Consisting of a Mild Transient Stroke followed by a Second Moderate Stroke in Rats(Elsevier, 2009) Qiao, M.; Zhao, Zonghang; Barber, Philip A.; Foniok, T.; Sun, S.; Tuor, Ursula I.Item Open Access Model of minor stroke with mild peri-infarct ischemic injury(Elsevier, 2016-04-29) Tuor, Ursula I.; Deng, Qinbo; Rushforth, Dave; Foniok, Taduesz; Qiao, MinBackground Transient ischemic attack, minor stroke and stroke recurrence need improved treatment but lack animal models for research. The aim was to modify photothrombosis methods thereby producing both a minor stroke (with adjacent mild damage) or a minor recurrent stroke. New method A minor stroke, as detected using magnetic resonance imaging and histology, was produced using a low intensity beam of white light with a bright centre, a low dose of Rose Bengal and a short 5 min illumination of thinned skull. A recurrent minor stroke was produced by repeating the procedure two days later except the cortical mask was positioned 1.5 mm posteriorly. Results The minor photothrombosis procedure produced a small superficial infarct surrounded by a region of scattered necrosis detected histologically. Marked hyperintensities in diffusion weighted and T2 images identified the infarct. Peri-infarct regions with modest T2 increases corresponded to regions of scattered cell death. A recurrent minor photothrombosis produced additional damage in regions with overlapping mild injury. Comparison with existing methods Previous photothrombosis methods usually produce large cortical infarcts with little penumbra. The current method produces small infarcts with diffuse mild peri-infarct ischemic injury that can be diagnosed using T2 imaging. Conclusions The modified photothrombotic procedure will produce a minor stroke consisting of a small infarct in a region with marked diffusion and T2 hyperintensities and a peri-infarct region of selective necrosis with modest T2 changes. Minor recurrent stroke is readily produced but imaging is key for assessing size and location of each insult. Abbreviations Dw, diffusion weighted; MRI, magnetic resonance imaging; Iba1, Ionized Calcium-Binding Adapter Molecule 1; T2w, transverse relaxation time weighted; TIA, transient ischemic attackItem Open Access Recurrent mild cerebral ischemia: enhanced brain injury following acute compared to subacute recurrence in the rat(Biomed Central Ltd., 2016-05-26) Tuor, Ursula I.; Zhao, Zonghang; Barber, Philip; Qiao, MinBackground In the current study, a transient cerebral ischemia producing selective cell death was designated a mild ischemic insult. A comparable insult in humans is a transient ischemic attack (TIA) that is associated with functional recovery but can have imaging evidence of minor ischemic damage including cerebral atrophy. A TIA also predicts a high risk for early recurrence of a stroke or TIA and thus multiple ischemic insults are not uncommon. Not well understood is what the effect of differing recovery times between mild ischemic insults has on their pathophysiology. We investigated whether cumulative brain damage would differ if recurrence of a mild ischemic insult occurred at 1 or 3 days after a first insult. Results A transient episode of middle cerebral artery occlusion via microclip was produced to elicit mild ischemic changes—predominantly scattered necrosis. This was followed 1 or 3 days later by a repeat of the same insult. Brain damage assessed histologically 7 days later was substantially greater in the 1 day recurrent group than the 3 days recurrent group, with areas of damage consisting predominantly of regions of incomplete infarction and pannecrosis in the 1 day group but predominantly regions of selective necrosis and smaller areas of incomplete infarction in the 3 days group (P < 0.05). Enhanced injury was reflected by greater number of cells staining for macrophages/microglia with ED1 and greater alterations in GFAP staining of reactive astrocytes in the 1 day than 3 days recurrent groups. The differential susceptibility to injury did not correspond to higher levels of injurious factors present at the time of the second insult such as BBB disruption or increased cytokines (tumor necrosis factor). Microglial activation, with potential for some beneficial effects, appeared greater at 3 days than 1 day. Also blood analysis demonstrated changes that included an acute increase in granulocytes and decrease in platelets at 1 day compared to 3 days post transient ischemia. Conclusions Dynamic changes in multiple inflammatory responses likely contribute to the time dependence of the extent of damage produced by recurrent mild ischemic insults. The time of mild stroke recurrence is crucial with early recurrence producing greater damage than subacute recurrence and this supports urgency for determining and implementing optimal stroke management directly after a TIA.Item Open Access Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke(BioMed Central, 2010-02-02) Jin, Albert Y.; Tuor, Ursula I.; Rushforth, David; Kaur, Jaspreet; Muller, Robert N.; Petterson, Jodie Lee; Boutry, Sébastien; Barber, Philip A.