Abstract: A method and compositions are provided for increased cerebral bioavailability of blood-born compositions by administering the composition of interest while increasing brain NO levels. This increase in NO levels may be accomplished by stimulating increased production of NO by eNOS, especially by administering L-arginine, by administering agents that increase NO levels independent of ecNOS, or by any combination of these methods. As NO is increased, cerebral blood flow is consequently increased, and drugs in the blood stream are carried along with the increased flow into brain tissue. By increased flow, the site of action will be exposed to more drug molecules. By stimulating increased NO production, administration of drugs that are not easily introduced to the brain may be facilitated and/or the serum concentration necessary to achieve desired physiologic effects may be reduced.

Abstract: This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided.

Abstract: A method and compositions are provided for increased cerebral bioavailability of blood-born compositions by administering the composition of interest while increasing brain NO levels. This increase in NO levels may be accomplished by stimulating increased production of NO by eNOS, especially by administering L-arginine, by administering agents that increase NO levels independent of ecNOS, or by any combination of these methods. As NO is increased, cerebral blood flow is consequently increased, and drugs in the blood stream are carried along with the increased flow into brain tissue. By increased flow, the site of action will be exposed to more drug molecules. By stimulating increased NO production, administration of drugs that are not easily introduced to the brain may be facilitated and/or the serum concentration necessary to achieve desired physiologic effects may be reduced.

Abstract: The invention relates to the use of epoxyeicosatrienoic acids and/or inducers of cytochrome P-450 epoxygenase activity to reduce brain injury in a subject with a cerebrovascular condition, including stroke.

Abstract: The invention relates to the use of MEK1 inhibitors to reduce tissue damage resulting from ischemia and/or reperfusion, particularly brain damage associated with ischemia resulting from stroke. Pharmaceutical compositions, kits and perfusion fluids including MEK1 inhibitors are also provided.

Abstract: Methods and compositions for the treatment of conditions which would benefit from vasoconstriction or the inhibition of vasoconstriction via modulation of sphingosine kinase and sphingosine-1-phosphate phosphatase activity and EDG receptor signaling are provided. These conditions include migraine, stroke, subarachnoid hemorrhage and vasospasm. Also provided are screening methods for modulators of sphingosine kinase and sphingosine-1-phosphate phosphatase activity and EDG receptor signaling which are capable of regulating vasoconstriction.

Abstract: This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided.

Abstract: The invention relates to the use of MEK1 inhibitors to reduce tissue damage resulting from ischemia and/or reperfusion, particularly brain damage associated with ischemia resulting from stroke. Pharmaceutical compositions, kits and perfusion fluids including MEK1 inhibitors are also provided.

Abstract: A new use for HMG-CoA reductase inhibitors is provided. In the instant invention, HMG-CoA reductase inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase activity through a mechanism other than preventing the formation of oxidative-LDL. As a result, HMG-CoA reductase inhibitors are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

Abstract: The present invention provides methods for treating migraine headache comprising administering an effective amount of a neurosteroid that directly or indirectly activates GABA.sub.A receptors.

Abstract: The present invention provides methods for treating migraine headache. The methods useful according to the invention involve the treatment of patients who experience symptoms of migraine headache with compounds that directly or indirectly activate GABA.sub.A receptors.

Abstract: Intravenous administration and pharmaceutically acceptable compositions of neurotrophic factors for treating neuronal damage in the central nervous system of individuals in need of such treatment are disclosed. The neuronal damage associated with ischemia, hypoxia, or neurodegeneration may result from stroke or cardiac arrest. This invention provides for the intravenous administration of neurotrophic factors such as bFGF, aFGF, NGF, CNTF, BDNF, NT3, NT4, IGF-I and IGF-II.

Abstract: A method for treatment of stroke in a patient, involving administering to the patient a nitric oxide-releasing compound. A preferred compound of the invention is L-arginine.