Prevention... after the insult?

In multiple previous studies evaluated by this class and blog, I have been critical of research methods that involve the administration of a drug or other treatment option before introducing the disease agent or disease state, such as in subjecting mice to stroke. I felt that while those studies may have cast new light on certain fields as proofs of concept, their clinical applications were minimal. The Candelario-Jalil et al. paper gives an incredibly thorough example of an inflammatory process that is affected differently by drugs given 30 minutes previous to an incident versus the same drugs given 6 hours after a transient global cerebral ischemia.

The adverse effects of global cerebral ischemia are biphasic, with a marked hike in hippocampal prostaglandin E2 (PGE2) 2 hours after the insult and another notable jump in PEG2 levels 24-48 hours after the transient ischemia. It was fortuitous that this study included so many animals and was planned with so many factors accounted, with administration of COX-1 and COX-2 inhibitors either before or after the ischemic event and in different doses, because their findings were significantly different for each drug at the different times of treatment. COX-1 inhibitors were more effective given before the ischemic event, as COX-1 was shown to play a stronger role in the hours directly following ischemia. In gerbils given COX-1 inhibitor six hours after ischemia, there was little improvement compared to sham gerbils. In contrast, COX-2 inhibitors exhibited better protection for hippocampal CA1 neurons at the 24-48 hour point following ischemia.

Had this study not looked at two different treatment timelines, would we have concluded that COX-1 inhibitors are entirely more effective at treating transient ischemia than COX-2 inhibitors? On the same note, two labs looking at the same drugs but with different timelines could publish diametrically opposed papers if they failed to evaluate the full course of disease progression. All this forces me to wonder if much of the conflicting material published in the scientific community is because of the narrow scope of certain studies which are then assumed to have wider application.

Candelario-Jalil, Eduardo, Armando Gonzalez-Falcon, Michel Garcia-Cabrera, Dalia Alvarez, Said Al-Dalain, Gregorio Martinez, Olga Sonia Leon, and Joe E. Springer. "Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia." Journal of Neurochemistry. 2003, 86, 545-555.