Present status and future challenges of electroencephalography- and magnetic resonance imaging-based monitoring in preclinical models of focal cerebral ischemia.

Animal models are useful tools for better understanding the mechanisms underlying neurological deterioration after an ischemic insult as well as subsequent evolution of changes and recovery of functions. In response to the updated requirements for preclinical investigations of stroke to include relevant functional measurement techniques and biomarker endpoints, we here review the state of knowledge on application of some translational electrophysiological and neuroimaging methods, and in particular, electroencephalography monitoring and magnetic resonance imaging in rodent models of ischemic stroke. This may lead to improvement of diagnostic methods and identification of new therapeutic targets, which would considerably advance the translational value of preclinical stroke research.

Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke.

Background: The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age.

Protective role for type 4 metabotropic glutamate receptors against ischemic brain damage.

We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10  mg/kg, subcutaneous, administered once 30  minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%.

Induction of the Wnt antagonist, Dickkopf-1, contributes to the development of neuronal death in models of brain focal ischemia.

Inhibition of the canonical Wnt pathway has been implicated in the pathophysiology of neuronal death. Here, we report that the secreted Wnt antagonist, Dickkopf-1 (Dkk-1) is rapidly induced in neurons after induction of focal brain ischemia. In rats undergoing transient focal ischemia in response to brain infusion of endothelin-1, Dkk-1 was induced in neurons of the ischemic core and the penumbra region.

Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia.

Transient focal ischemia produced by local infusion of endothelin-1 (ET1) in the territory of the middle cerebral artery has been proposed as a potentially useful model for the screening of drugs developed for the treatment of thrombo-embolic stroke. However, most of the data rely exclusively on the assessment of the infarct volume, which is only a partial predictor of the neurological outcome of stroke. Here, we have validated the model using a multimodal approach for the assessment of neuroprotection, which includes (i) determination of the infarct volume by 2,3,5-triphenyltetrazolium chloride staining; (ii) an in-depth behavioral analysis of the neurological deficit; and (iii) an EEG analysis of electrophysiological abnormalities in the peri-infarct somatosensory forelimb cortical area, S1FL.

Age-related changes in neocortical high-voltage spindles and alpha EEG power during quiet waking in rats.

Age-related changes in neocortical high-voltage spindle (HVS) and in electroencephalographic (EEG) alpha power were examined in young (3.0 to 4.6 months), middle-aged (10.