In the light of accumulating evidence for the occurrence of spontaneous cortical spreading depression and peri-infarct depolarizations in the human brain injured by trauma or aneurysmal subarachnoid haemorrhage, we used DC electrode recording and laser speckle imaging to study the relationship between depolarization events and perfusion in the ischaemic, gyrencephalic brain. In 14 adult male cats anaesthetized with chloralose, one cerebral hemisphere was exposed and the middle cerebral artery occluded. Surface cortical perfusion in core and penumbral territories was imaged semiquantitatively at intervals of 13 s for 4 h. Cortical surface DC potential was recorded. Time interval between changes in DC potential and in perfusion was examined, and this comparison was repeated using microelectrodes for DC potential in five similar experiments in a second laboratory. Mean pre-occlusion perfusion was 11707 +/- 4581 units (equivalent to CBF (cerebral blood flow) approximately 40.5 +/- SD 14.4 ml/100 g/min), and fell on occlusion to 5318 +/- 2916 (CBF approximately 17.1 +/- 8.3), 5291 +/- 3407 (CBF approximately 17.0 +/- 10.1), and 6711 +/- 3271 (CBF approximately 22.2 +/- 9.6), quickly recovering to 8704 +/- 4581 (CBF approximately 29.5 +/- 14.4), 9741 +/- 4499 (CBF approximately 33.3 +/- 14.1) and 10 314 +/- 3762 (CBF approximately 35.4 +/- 11.4) on the core, intermediate and outer penumbral gyri, respectively. Mean perfusion later fell secondarily on core and intermediate gyri but, overall, was preserved on the outer (upper level of perfusion) gyrus during the period of observation. Pattern and severity of transient changes in perfusion associated with depolarization events varied with gyral location; falls in perfusion were sometimes profound and irreversible, and followed rather than preceded depolarization. In this model of occlusive stroke, reductions in perfusion linked to peri-infarct depolarization events contribute to secondary deterioration in penumbral areas. The findings suggest that such events play a central rather than a subsidiary role in cerebral infarction in the gyrencephalic brain.

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Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozymeindependent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARγ agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.