Torpor during hibernation defines the nadir of mammalian metabolism where whole animal rates of metabolism are decreased to as low as 2% of basal metabolic rate. This capacity to decrease profoundly the metabolic demand of organs and tissues has the potential to translate into novel therapies for the treatment of ischemia associated with stroke, cardiac arrest or trauma where delivery of oxygen and nutrients fails to meet demand. If metabolic demand could be arrested in a regulated way, cell and tissue injury could be attenuated. Metabolic suppression achieved during hibernation is regulated, in part, by the central nervous system through indirect and possibly direct means. In this study, we review recent evidence for mechanisms of central nervous system control of torpor in hibernating rodents including evidence of a permissive, hibernation protein complex, a role for A1 adenosine receptors, mu opiate receptors, glutamate and thyrotropin-releasing hormone. Central sites for regulation of torpor include the hippocampus, hypothalamus and nuclei of the autonomic nervous system. In addition, we discuss evidence that hibernation phenotypes can be translated to non-hibernating species by H 2 S and 3-iodothyronamine with the caveat that the hypothermia, bradycardia, and metabolic suppression induced by these compounds may or may not be identical to mechanisms employed in true hibernation. Keywords metabolic arrest; metabolic suppression; suspended animationHibernating animals display a variety of adaptations that protect the central nervous system from metabolic challenges and trauma that are injurious in non-hibernating species. These adaptations include profound decreases in brain and body temperature (T b ) and immune function, enhanced antioxidant defenses, and metabolic suppression Zhou et al. 2001; Ross et al. 2006). Metabolic suppression, a regulated and reversible reduction in cellular and tissue need for oxygen and nutrients, matches metabolic demand with supply and is one of the most novel yet least well-understood neuroprotective aspects of hibernation. Knowledge of mechanisms used by hibernating animals to decrease metabolic demand to as low as 2% of basal metabolic rate or 0.01 mL O 2 /g/h

Oxygen-glucose deprivation (OGD) initiates a cascade of intracellular responses that culminates in cell death in sensitive species. Neurons from Arctic ground squirrels (AGS), a hibernating species, tolerate OGD in vitro and global ischemia in vivo independent of temperature or torpor. Regulation of energy stores and activation of mitogen-activated protein kinase (MAPK) signaling pathways can regulate neuronal survival. We used acute hippocampal slices to investigate the role of ATP stores and extracellular signal-regulated kinase (ERK)1/2 and Jun NH 2 -terminal kinase (JNK) MAPKs in promoting survival. Acute hippocampal slices from AGS tolerated 30 mins of OGD and showed a small but significant increase in cell death with 2 h OGD at 371C. This tolerance is independent of hibernation state or season. Neurons from AGS survive OGD despite rapid ATP depletion by 3 mins in interbout euthermic AGS and 10 mins in hibernating AGS. Oxygen-glucose deprivation does not induce JNK activation in AGS and baseline ERK1/2 and JNK activation is maintained even after drastic depletion of ATP. Surprisingly, inhibition of ERK1/2 or JNK during OGD had no effect on survival, whereas inhibition of JNK increased cell death during normoxia. Thus, protective mechanisms promoting tolerance to OGD by AGS are downstream from ATP loss and are independent of hibernation state or season.

No abstract

The present study examined the physiological mechanisms of the responses of brain tissue oxygen partial pressure (P t O 2 ), brain temperature (T brain ), global oxygen consumption V̇o 2 , and respiratory frequency (f R ) to hypoxia in non-sedated and non-anesthetized arctic ground squirrels (Spermophilus parryii, AGS) and rats. We found that 1) in contrast to oxygen partial pressure in blood (P a O 2 ), the baseline value of P t O 2 in summer euthermic AGS is significantly higher than in rats; 2) both P t O 2 and P a O 2 are dramatically reduced by inspired 8% O 2 in AGS and rats, but AGS have a greater capacity in P t O 2 to cope with environmental hypoxia; 3) metabolic rate before, during, and after hypoxic exposure is consistently lower in AGS than in rats; 4) the respiratory responding patterns to hypoxia in the two species differ in that f R decreases in AGS but increases in rats. These results suggest that 1) AGS have special mechanisms to maintain higher P t O 2 and lower P a O 2 , and these levels in AGS represent a typical pattern of adaptation of heterothermic species to and a brain protection from hypoxia; 2) AGS brain responds to hypoxia through greater decreases in P t O 2 and decreased f R and ventilation. In contrast, rat brain responds to hypoxia by less reduction in P t O 2 and increased f R and ventilation.

Polydimethylsiloxanes (PDMS) have been extensively utilized for their ability to spread and lubricate surfaces. This ability can be mostly attributed to their low surface energy and extremely flexible backbone. This study examines their unique ability through a comparative analysis of the rates of spread of numerous commercially available oils and lubricants, including a series of methylterminated PDMS. The analysis facilitated the design and synthesis of two homologous series of PDMS, in which the terminal ends were functionalized as quaternary ammonium salts. The two new series of compounds were examined for their ability to spread both as neat liquids and as formulated blends. Additionally, these hybrid ionic oligomers were screened for biological activity against Staphylococcus aureus. All of the new oligomers exhibited antimicrobial properties in preliminary testing.