Methods of increasing cerebral blood flow
View Patent ↗Methods of increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided. The method for increasing blood flow in such a mammalian brain blood vessel includes administering to a patient in need thereof a therapeutically effective amount of an inhibitor of δ protein kinase C. In certain embodiments, the inhibitor can be chronically administered without causing desensitization of the patient to the inhibitor. Kits for increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided.
1. A method of increasing blood flow in a mammalian brain blood vessel experiencing decreased blood flow, comprising administering to a patient a therapeutically effective amount of a peptide inhibitor of δ protein kinase C (δPKC), wherein said peptide is selected from the group consisting of SEQ ID NO: 67, SEQ NO: 68, SEQ NO:69, SEQ NO: 70, SEQ NO: 71, SEQ NO: 72, SEQ NO: 73, SEQ NO: 74, SEQ NO: 75, SEQ NO: 76, SEQ NO: 77, SEQ NO: 78, SEQ NO: 79, SEQ NO: 80, SEQ NO: 81, SEQ NO: 82, and SEQ NO: 83, wherein said patient is suffering from an ischemic event, reperfusion injury, vasoconstriction, vasospasm, stroke, or chronic high blood pressure.
2. The method of claim 1 , wherein said blood vessel has been subjected to an ischemic or reperfusion event.
3. The method to claim 1 , wherein said blood vessel has been subjected to vasoconstriction or vasospasm.
4. The method of claim 2 , wherein the blood flow is increased in an ischemic penumbra arising from said ischemic event compared to the blood flow during said ischemic event.
5. The method of claim 3 , wherein the blood flow is increased in a hypoperfused area due to vasoconstriction or vasospasm compared to the blood flow during said vasoconstriction or vasospasm.
6. The method of claim 1 , wherein said blood vessel is a cerebral artery, capillary, or arteriole.
7. The method of claim 6 , wherein said cerebral artery is an anterior cerebral artery, a middle cerebral artery or a posterior cerebral artery.
8. The method of claim 1 , wherein said blood vessel is a carotid artery.
9. The method of claim 1 , wherein said therapeutically effective amount of an inhibitor of δ protein kinase C is an amount effective in increasing blood flow at least about 10% relative to blood flow prior to administering said inhibitor.
10. The method of claim 1 , wherein said therapeutically effective amount of an inhibitor of δPKC is an amount effective in increasing blood flow at least 50% relative to blood flow prior to administering said inhibitor.
11. The method of claim 1 , wherein said inhibitor is administered by a parenteral route.
12. The method of claim 1 , wherein said inhibitor is capable of chronic administration without causing desensitization to said inhibitor.
13. The method of claim 12 , wherein said inhibitor is administered multiple time to a patient.
14. A method of increasing blood flow in a mammalian brain blood vessel experiencing decreased blood flow, comprising administering to a patient a therapeutically effective amount of a peptide inhibitor of δ protein kinase C (δPKC), wherein said peptide inhibitor of δPKC is attached to a cell permeable carrier peptide, and wherein said peptide inhibitor of δPKC is selected from the group consisting of SEQ ID NO: 67, SEQ NO: 68, SEQ NO:69, SEQ NO: 70, SEQ NO: 71, SEQ NO: 72, SEQ NO: 73, SEQ NO: 74, SEQ NO: 75, SEQ NO: 76, SEQ NO: 77, SEQ NO: 78, SEQ NO: 79, SEQ NO: 80, SEQ NO: 81, SEQ NO: 82, and SEQ NO: 83, wherein said patient is suffering from an ischemic event, reperfusion injury, vasoconstriction, vasospasm, stroke, or chronic high blood pressure.
15. The method of claim 14 , wherein said cell permeable carrier peptide is selected from the group consisting of a Drosophilia Antennapedia homeodomain peptide, a Transactivating Regulatory Protein (Tat) peptide, and a polyarginine peptide.
16. The method of claim 14 , wherein said blood vessel is a cerebral artery, capillary, or arteriole.
17. The method of claim 14 , wherein said cerebral artery is an anterior cerebral artery, a middle cerebral artery or a posterior cerebral artery.
18. The method of claim 14 , wherein said blood vessel is a carotid artery.
19. The method of claim 14 , wherein said peptide inhibitor is administered by a parenteral route.
20. The method of claim 14 , wherein said peptide inhibitor is capable of chronic administration without causing desensitization to said inhibitor.
21. The method of claim 14 , wherein said peptide inhibitor is administered multiple times to a patient.