Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits.

Recent electrophysiological studies have suggested surges in electrical correlates of consciousness (i.e., elevated gamma power and connectivity) after cardiac arrest (CA). This study examines electrocorticogram (ECoG) activity and coherence of the dying brain during asphyxial CA. Male Wistar rats (n = 16) were induced with isoflurane anesthesia, which was washed out before asphyxial CA. Mean phase coherence and ECoG power were compared during different stages of the asphyxial period to assess potential neural correlates of consciousness. After asphyxia, the ECoG progressed through four distinct stages (asphyxial stages 1-4 [AS1-4]), including a transient period of near-electrocerebral silence lasting several seconds (AS3). Electrocerebral silence (AS4) occurred within 1 min of the start of asphyxia, and pulseless electrical activity followed the start of AS4 by 1-2 min. AS3 was linked to a significant increase in frontal coherence between the left and right motor cortices (p < 0.05), with no corresponding increase in ECoG power. AS3 was also associated with a significant posterior shift of ECoG power, favoring the visual cortices (p < 0.05). Although the ECoG during AS3 appears visually flat or silent when viewed with standard clinical settings, our study suggests that this period of transient near-electrocerebral silence contains distinctive neural activity. Specifically, the burst in frontal coherence and posterior shift of ECoG power that we find during this period immediately preceding CA may be a neural correlate of conscious processing.