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 T increase 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 T and 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 T and 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 T and 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 T and 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.

Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke

“…We used perfusion, diffusion, and T 2 -weighted MRI techniques that are commonly used to characterize ischemic core and estimate penumbra. 18–21 To more specifically assess the role of collaterals and exclude confounding reperfusion factors, we used MRI at 1, 5, and 24h after pMCAo. To corroborate the MR findings, we performed cleaved caspase-3 (CC3) and heme oxygenase-1 (HO-1) immunohistochemistry in a subset of animals to quantify ischemic core and penumbra, respectively.…”

Mean Diffusivity in Striatum Correlates With Acute Neuronal Death but Not Lesser Neuronal Injury in a Pilot Study of Neonatal Piglets With Encephalopathy

“…Because the ability to detect brain injury by MRI varies by patient age 13 and time from the sentinel injury, 2 the accuracy of clinical MRI for detecting early and emerging HIE is unclear. Nascent irreversible or reversible neuronal injury, small proportions of selectively vulnerable neurons, and a mix of infarcted and noninfarcted regions soon after HI may raise the complexity of MRI interpretation.…”

Characterizing the Evolution of Lesion, Penumbra and Blood-Brain Barrier Permeability in a Photothrombotic Juvenile Rat Stroke Model Using MRI and Histology

“…Another important consideration revealed in experimental studies of stroke is the changes in BBB permeability from the acute, sub-acute and chronic phases following stroke ictus. Several longitudinal animal studies have shown an 'open-close-open' biphasic pattern in which the BBB has increased permeability at the rst stage, followed by a return to normal values and a second permeability increase [44][45][46]. More recent literature points to a more continuous opening of the BBB with biphasic permeability peaks but without total closing [47][48][49].…”