title: Magnetic resonance imaging of ischemic injury produced by varying severities of photothrombosis differs in neonatal and adult brain.
abstract: Stroke is a major cause of disability in adults and children. Recently, we have developed an adult rat model of minor stroke containing a peri-infarct region with a modest T2increase and mild ischemic damage. We hypothesized that a neonatal minor stroke with mild peri-ischemic changes could also be produced, but with potential ontogenic differences. Using our minor photothrombosis method, we produced a range of severities of ischemic lesions (mini, minor, moderate and severe) within magnetic resonance imaging (MRI) slices of adult and neonatal rats. In both age groups, the lesion region showed a marked increase in T2and diffusion-weighted intensity and decrease in apparent diffusion coefficient (ADC), corresponding to a cortical infarct detected using fluorojade and hematoxylin and eosin staining. Perilesional regions showed modest increases in T2and ADC in adults, but not neonates, and this corresponded to scattered cell death, but not necessarily extravasation of plasma protein, i.e. blood-brain barrier disruption. Mini and minor insults in neonates generally showed homogeneous and rather modest changes in T2and ADC. MR perfusion maps demonstrated a penumbral area of greater hypoperfusion in adults compared with neonates. Together, the results indicate that, in neonatal cortex, a similar severity of photothrombosis occurs throughout the area of photoactivation, whereas, in adult brain, spontaneous clot lysis and/or partial thrombosis occurs adjacent to permanently occluded vessels. Thus, by comparing differing severities of photothrombotic ischemia in neonates and adults, ontogenic differences were detectable using MRI, with mature brain having a greater penumbral region. Mild ischemic injury and scattered cell death in both neonates and adults could be identified by a modest increase in T2and decrease in ADC. A better understanding of the effects of development on ischemic responses and associated MRI changes will provide a basis for the improved diagnosis of mild or minor ischemic insults relevant to pediatric and adult stroke.
authors.affiliation: Physiology and Pharmacology and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.|Experimental Imaging Center, University of Calgary, Calgary, Canada.
authors.forename: Ursula I
authors.initials: UI
authors.lastname: Tuor
authors.affiliation: Physiology and Pharmacology and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Physiology and Pharmacology and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Manasi
authors.initials: M
authors.lastname: Sule
authors.affiliation: Physiology and Pharmacology and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Morgunov
authors.affiliation: Experimental Imaging Center, University of Calgary, Calgary, Canada.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Foniok
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013927:Thrombosis / Q000150:complications* / Q000000981:diagnostic imaging* / Q000473:pathology*
keywords: T2; animal model study; brain ischemia and degeneration; diffusion; fetal and pediatric neurological diseases