Can 12/15-Lipoxygenase Inhibition Protect Against Increased Brain Injury After Experimental Stroke in Diabetic Animals?

In addition to conferring a higher risk of stroke and cardiovascular events, diabetes mellitus also leads to increased severity of stroke and worse outcome. The reasons for this are not entirely clear, but relate to deficiencies in the brain vasculature of diabetics. Our lab has previously shown that the enzyme 12/15-lipoxygenase (12/15-LOX) is a major contributor to both neuronal cell death, as well as vascular injury and edema formation following experimental stroke in mice (van Leyen et al., Stroke 2006; Jin et al., Stroke 2008). Using the db/db mouse as a model for type 2 diabetes, we have now generated Preliminary Data to show that 12/15-LOX is increased on the ischemic side of the brain in a stroke model of distal middle cerebral artery occlusion, in what appears to be vascular cells. Our Central Hypothesis states that 12/15-LOX, which is known to be up-regulated in diabetes, is a major contributor to vascular failure and increased brain injury following stroke in diabetic animals.