Adenosinergic modulation of CA1 neuronal tolerance to glucose deprivation in organotypic hippocampal cultures.
Glucose deprivation produced neuronal degeneration of CA1 pyramidal neurons in hippocampal slice cultures. The effects of the adenosine agonist cyclohexyladenosine (CHA) and antagonist cyclopentylxanthine (CPX) on CA1 neuronal loss following hypoglycemia was examined using propidium iodide fluorescence as an indicator of cell death. The intensity of propidium iodide fluorescence in hippocampal area CA1 was quantified using Optimas image analysis software. Following 2 or 3 h of glucose deprivation, CPX significantly enhanced injury in the CA1 region while CHA provided significant protection. These results suggest that adenosine plays an important role in endogenous neuronal protection during hypoglycemic injury, and also supports a role for the use of adenosine agonists as neuroprotective agents.
Hsu
S S
SS
Department of Neurological Surgery, University of Washington School of Medicine, Seattle 98104.
Newell
D W
DW
Tucker
A
A
Malouf
A T
AT
Winn
H R
HR
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D007003:Hypoglycemia / Q000473:pathology; D009410:Nerve Degeneration; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; D005947:Glucose; D000241:Adenosine