A new model of ischemic preconditioning using young adult hippocampal slice cultures.
In ischemic preconditioning (IPC), brief sublethal ischemia protects neurons from a subsequent lethal ischemia. In vivo models faithfully display preconditioning, yet, these models are technically challenging, time-consuming and expensive. In vitro models of preconditioning have also been developed that are technically easier and less expensive. A drawback of pre-existing in vitro models is that since susceptibility to ischemic injury is age-dependent; neuroprotection is being studied in neurons that have intrinsic resistance to oxygen-glucose deprivation (OGD). This study introduces a new in vitro model of ischemic preconditioning in hippocampal slice cultures isolated from 20-30-day-old rats. Slice cultures show a high susceptibility and sharp thresholds toward ischemia that is comparable to that found in vivo. A 5-min OGD treatment was not neurotoxic to young adult slice cultures, while a 10-min OGD treatment was neurotoxic. In addition, the sublethal 5-min OGD treatment protected against a 10-min OGD treatment that was delivered 24 h later. Neuroprotection was seen in preconditioned slice cultures stained with propidium iodide (PI) or with antisera against the neuron-specific antigen NeuN. Energy failure is hypothesized to trigger ischemic preconditioning and a 5-min OGD treatment induced transient energy failure in young adult slice cultures. This model may assist in the search for new therapeutics for the prevention and/or treatment of stroke.
Department of Physiology and Pharmacology, State University New York-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Getaw W
GW
Hassen
Dezhi
D
Tian
Ding
D
Ding
Peter J
PJ
Bergold
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004268:DNA-Binding Proteins; D015194:Diffusion Chambers, Culture; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods; D011419:Propidium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D011419:Propidium; D000255:Adenosine Triphosphate; D005947:Glucose