Ischemic preconditioning: a long term survival study using behavioural and histological endpoints

In this study we sought to determine if ischemic preconditioning provided long term behavioral and histological protection. A second goal was to see if ischemic preconditioning conveys its protective effect on CA1 neurons by altering post-ischemic brain temperature. While preconditioning episodes of short duration ischemia (i.e. 1.5 min) provided significant histological protection of CA1 pyramidal cells against a subsequent severe ischemic insult (i.e. 5 min), this did not result in complete behavioural protection. Preconditioned ischemic animals initially displayed habituation deficits in an open field test that were comparable to untreated ischemic gerbils. A significant decline in CA1 preservation in preconditioned animals was observed when survival time was extended from 10 (81% protection) to 30 (53% protection) days. In addition, protection was not observed in the subiculum and CA2 sector of the hippocampus where consistent damage was observed in 21/22 gerbils. Ischemic preconditioning did not markedly affect post-ischemic brain temperature suggesting that the observed protection was not due to a reduction in temperature during or after the severe ischemic insult. The lack of functional protection within the first 10 days after ischemia, along with the decline of cellular preservation over time, suggests that this paradigm may not provide permanent protection.