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Background and Purpose-Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia. Methods-Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately. Results-The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core. Conclusions-Functional stimulation of ischemic tissue may decrease tissue damage and improve outcome from stroke.Although the precise mechanism of this effect remains to be determined, functional stimulation could readily be translated to clinical practice. Key Words: cerebral ischemia, focal Ⅲ electrical stimulation therapy Ⅲ middle cerebral artery occlusion T here remains intense interest in discovering novel neuroprotective therapies for use in acute cerebral ischemia. Most recent research efforts have focused on compounds designed to interfere with the cascade of deleterious events that occur in tissue during and in the minutes and hours after cerebral ischemia. 1 Although many compounds have been investigated, to-date none have proven clinically useful in humans. 2,3 Nonpharmacological treatment techniques, such as hypothermia and hyperoxemia, have also been proposed, 4 but it remains to be seen how they transfer from laboratory to bedside. There are even studies suggesting that electrical stimulation of the cerebellar fastigial nucleus 5,6 before ischemia, or the spinal cord 7-9 weeks and months after the ischemic insult can reduce damage.Functional stimulation is accompanied by an increase in regional cerebral blood flow (CBF) in activated brain regions. We have shown previously in a rat model of graded cerebral ischemia that when CBF is reduced by as much as 90%, forepaw stimulation is still able to elicit an increase in blood flow in the somatosensory cortex, 10 and studies in stroke patients demonstrate that CBF can be activated...

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The fractional Brownian motion is a generalization of ordinary Brownian motion, used particularly when long-range dependence is required. Its explicit introduction is due to B.B. Mandelbrot and J.W. van Ness (1968) as a self-similar Gaussian process W (H) (t) with stationary increments. Here self-similarity means that (a −H W (H) (at) : t ≥ 0) d = (W (H) (t) : t ≥ 0), where H ∈ (0, 1) is the Hurst parameter of fractional Brownian motion.F.B. Knight gave a construction of ordinary Brownian motion as a limit of simple random walks in 1961. Later his method was simplified by P. Révész (1990) and then by the present author (1996). This approach is quite natural and elementary, and as such, can be extended to more general situations. Based on this, here we use moving averages of a suitable nested sequence of simple random walks that almost surely uniformly converge to fractional Brownian motion on compacts when H ∈ ( 1 4 , 1). The rate of convergence proved in this case is O(N − min(H− 1 4 , 1 4 ) log N ), where N is the number of steps used for the approximation.If the more accurate (but also more intricate) Komlós, Major, Tusnády (1975, 1976 approximation is used instead to embed random walks into ordinary Brownian motion, then the same type of moving averages almost surely uniformly converge to fractional Brownian motion on compacts for any H ∈ (0, 1). Moreover, the convergence rate is conjectured to be the best possible O(N −H log N ), though only O(N − min(H, 1 2 ) log N ) is proved here.