Methods and compositions for the treatment of ischemic injury to tissue using therapeutic hypothermia

Abstract

Disclosed are compositions and methods for inducing therapeutic hypothermia in a subject.

1 . A method of treating ischemic stroke in a subject comprising administering to the subject a therapeutically effective amount of one or more A 1  adenosine receptor (A 1 AR) agonists and one or more A 1 AR antagonists. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , further comprising inducing therapeutic hypothermia in the subject. 
     
     
         4 . The method of  claim 3 , further comprising maintaining hypothermia in the subject. 
     
     
         5 . The method of  claim 4 , wherein maintaining hypothermia in the patient comprises repeating the administration of the one or more A 1 AR agonists and one or more A 1 AR antagonists. 
     
     
         6 . The method of  claim 1 , wherein the A 1 AR agonist crosses the blood brain barrier. 
     
     
         7 . The method of  claim 6 , wherein the A 1 AR agonist is N 6 -cyclohexyladenosine (CHA) or capadenoson. 
     
     
         8 . The method of  claim 1 , wherein the A 1 AR antagonist does not cross the blood-brain barrier. 
     
     
         9 . The method of  claim 8 , wherein the A 1 AR antagonist is 8-p-sulfophenyltheophylline (8-SPT). 
     
     
         10 . The method of  claim 10 , wherein the one or more A 1 AR agonists and the one or more A 1 AR antagonists are co-administered. 
     
     
         11 . The method of  claim 1 , wherein the one or more A 1 AR antagonists is titrated to minimize side effects of the agonist. 
     
     
         12 . The method of  claim 1 , wherein the A 1 AR agonist is N 6 -cyclohexyladenosine (CHA) or capadenoson and the A 1 AR antagonist is 8-p-sulfophenyltheophylline (8-SPT). 
     
     
         13 - 20 . (canceled)