Compounds and methods for treatment of stroke
The present invention relates to methods and agents useful for the treatment of stroke, including ischemic stroke and hemorrhagic stroke. In particular, methods and agents for treating stroke in a subject are provided, wherein the agent is administered prior to diagnosis of the stroke as an ischemic stroke or a hemorrhagic stroke.
1. A method for treating a subject suspected of having had a stroke, prior to diagnosis of the stroke as an ischemic stroke or a hemorrhagic stroke, the method comprising the steps of:
a) administering a first dose of a compound which inhibits hypoxia inducible factor (HIF) prolyl hydroxylase activity to the subject; and
b) subsequently diagnosing the stroke as an ischemic stroke or a hemorrhagic stroke,
wherein if the subject is subsequently diagnosed as having had an ischemic stroke, the method further comprises the additional step of: administering a thrombolytic agent to the subject, wherein the administering of the thrombolytic agent occurs at least 3 hours after onset of the stroke.
2. The method of claim 1 , wherein the compound is a 2-oxoglutarate mimetic.
3. The method of claim 1 , wherein the treating comprises amelioration of brain tissue damage.
4. The method of claim 3 , wherein the brain tissue damage is selected from the group consisting of infarct volume, edema, neuronal degeneration, a lesion, and brain tissue loss.
5. The method of claim 1 , wherein the step of administering for first dose occurs at least 'hours after onset of the stroke.
6. The method of claim 1 , wherein the thrombolytic agent is tissue plasminogen activator (tPA).
7. The method of claim 1 , wherein the subject is subsequently diagnosed as having had an ischemic stroke and the method further comprises the additional step of: administering a second dose of compound at or subsequent to reperfusion.
8. The method of claim 7 , wherein the administering of the second dose of the compound occurs at least 24 hours after administrating the first dose.
9. The method of claim 1 , wherein the subject has diabetes.
10. The method of claim 1 , wherein the compound is a heterocyclic carboxamide.