Model of minor stroke with mild peri-infarct ischemic injury.

BACKGROUND: 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 5min illumination of thinned skull. A recurrent minor stroke was produced by repeating the procedure two days later except the cortical mask was positioned 1.5mm 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.

Blood-oxygen-level-dependent magnetic resonance signal and cerebral oxygenation responses to brain activation are enhanced by concurrent transient hypertension in rats.

Neuronal activation results in increases in blood-oxygen-level-dependent (BOLD) signal increases in magnetic resonance images, increases in cerebral blood flow (CBF), and changes in tissue oxygenation. We hypothesized that transient hypertension concurrent with neuronal activation would interfere with the normal physiological responses to neuronal activation potentially leading to additive responses. Anesthetized rats were prepared for functional magnetic resonance imaging studies in which increases in BOLD signal were measured in response to: (1) electrical forepaw stimulation, (2) different graded levels of transient hypertension produced with norepinephrine, and both 1 and 2. In other experiments with a similar protocol, changes in CBF and cortical oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) were measured using Laser Doppler Flowmetry and near-infrared (IR) spectroscopy. BOLD signal within the sensory-motor cortex increased during forepaw stimulation. These matched increases in CBF and oxyHb and decreases in deoxyHb. During moderate or severe transient hypertension, there was a blood pressure-dependent increase in BOLD signal, CBF, and oxyHb; and a decrease in deoxyHb. When transient hypertension and forepaw stimulation were combined, the responses of oxyHb, deoxyHb, or BOLD signal were generally a summation of each response. In contrast, the CBF response to forepaw stimulation was relatively unaffected by transient hypertension. We conclude that during stimulation with concurrent hypertension, the normal changes in tissue oxygenation that accompany neuronal activation are enhanced by the increases produced by hypertension despite an excellent autoregulation of CBF. The latter could reflect highly transient decreases in oxygen consumption or likely a redistribution of flow through more nonexchange vessels.