Sensory stimulation-based protection from impending stroke following MCA occlusion is correlated with desynchronization of widespread spontaneous local field potentials

Abstract

In a rat model of ischemic stroke by permanent occlusion of the medial cerebral artery (pMCAo), we have demonstrated using continuous recordings by microelectrode array at the depth of the ischemic territory that there is an immediate wide-spread increase in spontaneous local field potential synchrony following pMCAo that was correlated with ischemic stroke damage, but such increase was not seen in control sham-surgery rats. We further found that the underpinning source of the synchrony increase is intermittent bursts of low multi-frequency oscillations. Here we show that such increase in spontaneous LFP synchrony after pMCAo can be reduced to pre-pMCAo baseline level by delivering early (immediately after pMCAo) protective sensory stimulation that reduced the underpinning bursts. However, the delivery of a late (3 h after pMCAo) destructive sensory stimulation had no influence on the elevated LFP synchrony and its underpinning bursts. Histology confirmed both protection for the early stimulation group and an infarct for the late stimulation group. These findings highlight the unexpected importance of spontaneous LFP and its synchrony as a predictive correlate of cerebral protection or stroke infarct during the hyperacute state following pMCAo and the potential clinical relevance of stimulation to reduce EEG synchrony in acute stroke.

Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion

“…Our results support the hypothesis that the lactate shuttle is also a necessary complementary underpinning mechanism for sensory-based neuroprotection in the rat model of ischemic stroke and highlights the importance of sensory-activated astrocytes in neuroprotection. These findings, together with our previous findings that show how sensory stimulation minimizes the post-pMCAo build-up of infarct-predicting widespread cortical synchrony of spontaneous local field potentials (LFPs) 23 , 24 , demonstrate how protection from impending ischemic stroke by sensory stimulation is multidimensional involving all components of NGV from the collateral system to ANLS and neuronal activity.…”

“…Such LFP synchronization following pMCAo is the result of underlying synchronous bursts of low frequencies oscillations 23 . The continuous buildup of such synchronization over time results in an infarct, unless whisker stimulation is delivered to the ischemic cortex during the 2 h protective window resulting in desynchronization of the correlated LFPs and protection from impending infarct as verified by postmortem histology 24 . The widespread synchrony of low frequency bursts underlying the LFP synchrony buildup following pMCAo could also contribute to high energy demand to support this synchronous burst activity, which in turn could therefore also result in increase in demand for lactate.…”

Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion

“…Our results support the hypothesis that the lactate shuttle is also a necessary complementary underpinning mechanism for sensory-based neuroprotection in the rat model of ischemic stroke and highlights the importance of sensory-activated astrocytes in neuroprotection. These ndings, together with our previous ndings that show how sensory stimulation minimizes the post-pMCAo build-up of infarct-predicting widespread cortical synchrony of spontaneous local eld potentials (LFPs) 23,24 , demonstrate how protection from impending ischemic stroke by sensory stimulation is multidimensional involving all components of NGV from the collateral system to ANLS and spontaneous neuronal activity.…”

“…Such LFP synchronization following pMCAo is the result of underlying synchronous bursts of low frequencies oscillations 23 . The continuous buildup of such synchronization over time results in an infarct, unless whisker stimulation is delivered during the 2h protective window resulting in desynchronization of the LFPs and protection from impending infarct as veri ed by postmortem histology 24 . The widespread synchrony of low frequency bursts underlying the LFP synchrony buildup following pMCAo could also lead to high energy demand to support this synchronous burst activation, which in turn could therefore also result in increase of astrogliosis and reactive astrocytes.…”