Inhibitors of ncca-atp channels for therapy

Abstract

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.