INHIBITORS OF NCCA-ATP CHANNELS FOR THERAPY
Methods and compositions are provided that are utilized for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury. In particular, the methods and compositions are inhibitors of a particular NC Ca-ATP channel and include, for example, inhibitors of SUR1 and/or inhibitors of TRPM4. Kits for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury, are also provided. The present invention also concerns treatment and/or prevention of intraventricular hemorrhage in infants, including premature infants utilizing one or more inhibitors of the channel is provided to the infant, for example to brain cells of the infant.
1 .- 48 . (canceled)
49 . A method of inhibiting increase in extravasated blood in brain tissue of a subject comprising administering an effective amount of glibenclamide to the subject.
50 . The method of claim 49 , wherein the glibenclamide is administered intravenously.
51 . The method of claim 49 , wherein the glibenclamide is administered by injection.
52 . The method of claim 49 , wherein the glibenclamide is administered at a dose of about 3 mg/day.
53 . The method of claim 49 , wherein the administering comprising administering
(a) a bolus injection of glyburide of 15.7 ug to 665 ug; and
(b) an infusion dose of 0.3 ug/min to 11.8 ug/min glyburide for 3 days to 7 days.
54 . A method of reducing lesion volume post brain impact in a subject comprising administering an effective amount of glibenclamide to the subject.
55 . The method of claim 54 , wherein the glibenclamide is administered intravenously.
56 . The method of claim 54 , wherein the glibenclamide is administered by injection.
57 . The method of claim 54 , wherein the glibenclamide is administered at a dose of about 3 mg/day.
58 . The method of claim 54 , wherein the administering comprising administering
(a) a bolus injection of glyburide of 15.7 ug to 665 ug; and
(b) an infusion dose of 0.3 ug/min to 11.8 ug/min glyburide for 3 days to 7 days.
59 . A method of treating progressive hemorrhagic necrosis in a subject comprising administering an effective amount of glibenclamide to the subject.
60 . The method of claim 59 , wherein the glibenclamide is administered intravenously.
61 . The method of claim 59 , wherein the glibenclamide is administered by injection.
62 . The method of claim 59 , wherein the glibenclamide is administered at a dose of about 3 mg/day.
63 . The method of claim 59 , wherein the administering comprising administering
(a) a bolus injection of glyburide of 15.7 ug to 665 ug; and
(b) an infusion dose of 0.3 ug/min to 11.8 ug/min glyburide for 3 days to 7 days.
64 . A method of treating progressive secondary hemorrhage in a subject comprising administering an effective amount of glibenclamide to the subject.
65 . The method of claim 64 , wherein the glibenclamide is administered intravenously.
66 . The method of claim 64 , wherein the glibenclamide is administered by injection.
67 . The method of claim 64 , wherein the glibenclamide is administered at a dose of about 3 mg/day.
68 . The method of claim 64 , wherein the administering comprising administering
(a) a bolus injection of glyburide of 15.7 ug to 665 ug; and
(b) an infusion dose of 0.3 ug/min to 11.8 ug/min glyburide for 3 days to 7 days.