title: Arctic ground squirrel hippocampus tolerates oxygen glucose deprivation independent of hibernation season even when not hibernating and after ATP depletion, acidosis, and glutamate efflux.
abstract: Cerebral ischemia/reperfusion (I/R) triggers a cascade of uncontrolled cellular processes that perturb cell homeostasis. The arctic ground squirrel (AGS), a seasonal hibernator resists brain damage following cerebral I/R caused by cardiac arrest and resuscitation. However, it remains unclear if tolerance to I/R injury in AGS depends on the hibernation season. Moreover, it is also not clear if events such as depletion of ATP, acidosis, and glutamate efflux that are associated with anoxic depolarization are attenuated in AGS. Here, we employ a novel microperfusion technique to test the hypothesis that tolerance to I/R injury modeled in an acute hippocampal slice preparation in AGS is independent of the hibernation season and persists even after glutamate efflux. Acute hippocampal slices were harvested from summer euthermic AGS, hibernating AGS, and interbout euthermic AGS. Slices were subjected to oxygen glucose deprivation (OGD), an in vitro model of I/R injury to determine cell death marked by lactate dehydrogenase (LDH) release. ATP was assayed using ENLITEN ATP assay. Glutamate and aspartate efflux was measured using capillary electrophoresis. For acidosis, slices were subjected to pH 6.4 or ischemic shift solution (ISS). Acute hippocampal slices from rats were used as a positive control, susceptible to I/R injury. Our results indicate that when tissue temperature is maintained at 36°C, hibernation season has no influence on OGD-induced cell death in AGS hippocampal slices. Our data also show that tolerance to OGD in AGS hippocampal slices occurs despite loss of ATP and glutamate release, and persists during conditions that mimic acidosis and ionic shifts, characteristic of cerebral I/R. Read the Editorial Comment for this article on page 10.
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, USA.|Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, USA.
authors.forename: Saurav
authors.initials: S
authors.lastname: Bhowmick
authors.affiliation: Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, USA.
authors.forename: Jeanette T
authors.initials: JT
authors.lastname: Moore
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kirschner
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, USA.|Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Drew
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D016923:Cell Death; D005947:Glucose / Q000172:deficiency*; D018698:Glutamic Acid / Q000378:metabolism*; D006605:Hibernation / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012589:Sciuridae / Q000502:physiology*; D012621:Seasons; D013696:Temperature
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005947:Glucose
keywords: 
  in vitro
  ; hibernation; hippocampal brain slices; ischemia; lactate dehydrogenase release; oxygen glucose deprivation