Stroke remains the second leading cause of death worldwide. The major problem is that the therapeutic window is short and no accepted treatment is completely efficient. Even though there is evidence of free radical participation in the pathophysiology of stroke, no beneficial effects of antioxidants have been demonstrated in clinical assays. Moreover, some reports paradoxically indicate that antioxidants could be harmful and that oxidative stress preconditioning could reduce the long-term effects of stroke. There are two major areas within the ischaemic zone: (1) the core, where neuronal necrosis develops in minutes, and (2) the penumbra surrounding the core, where some neurons could eventually be recovered over an extended time. The present review specifically focuses on the role of free radicals in the life or death of brain cells (mainly neurons) within the ischaemic penumbra. It also analyses the effects of oxidative stress on blood-brain barrier disruption. In conclusion, we postulate a cascade of events that follow cerebral ischaemia and what type of therapeutic approach could eventually change the effect of free radicals on neuronal recovery from an ischaemic penumbra.
Part of the book: Free Radicals and Diseases
The antioxidant properties of dimethylformamide (DMF) depend on its interference with the hydroxyl-radical-transduction pathway. Diabetes is a risk factor of cerebral ischaemia (CI), and both entities are associated with oxidative stress (OS). We evaluated DMF’s effects on CI in non-diabetic rats (NDRs) and in diabetic rats (DRs). One hour after CI, the animals were divided into two treatment groups (300 μl subcutaneous): either DMF or isotonic saline solution. Treatment effects were analysed in NDRs or DRs without CI. Eight hours after CI, a neurophysiologic score (NS) was determined; CI and OS biomarkers were measured in the ischaemic cerebral hemisphere. Infarct/oedema volumes were measured on dyed brain slices. DMF reduced infarct volume in NDRs and DRs but only improved the NS in DRs. Basal concentrations of all the biomarkers were similar in the NDRs and DRs. Metalloproteinase 9 (MMP9) did not change with DMF. Malondialdehyde (MDA) increased with CI, and DMF only reduced it in DRs. RAGE, nitrite/nitrate and nitrotyrosine increased with CI only in DRs (all prevented by DMF). We conclude that DMF’s benefits on CI were greater in the DRs due to a higher susceptibility of diabetic animals to the OS produced by CI. The results open a new horizon in CI treatment since DMF has not been investigated before.
Part of the book: Free Radicals, Antioxidants and Diseases