Method and compositions for treating stroke with fever

Abstract

The invention provides methods of treating stroke and related conditions exacerbated by fever and/or hyperglycemi by administering peptides or peptidomimetics that inhibit binding of NMDAR 2B to PSD-95 to a patient.

1 - 25 . (canceled) 
     
     
         26 . A method of screening a compound that inhibits binding of PSD-95 to NDMAR, comprising
 administering the compound to a animal having ischemia exacerbated by hyperthermia and/or hyperglycemia; and   determining whether the compound reduces infarction volume resulting from the ischemia relative to a control animal not treated with the compound.   
     
     
         27 . The method of  claim 26 , wherein the ischemia is a permanent ischemia. 
     
     
         28 . The method of  claim 27 , wherein the animal has hyperglycemia before administering the compound. 
     
     
         29 . The method of  claim 27 , wherein the animal has an infection. 
     
     
         30 . The method of  claim 27 , wherein the animal has diabetes. 
     
     
         31 . The method of claim  20 , wherein the animal has eaten less than twelve hours before administering the compound 
     
     
         32 . A method for reducing the damaging effect of stroke in a patient having stroke or other injury to the CNS exacerbated by fever comprising administering to the an effective amount of a peptide having an amino acid sequence comprising ESDV (SEQ ID NO:3) or ETDV (SEQ ID NO:5), wherein the peptide is linked to an internalization peptide or derivatized to improve the ability of the peptide to cross a membrane, and thereby reducing the damaging effect of the stroke or traumatic injury to the CNS, wherein the patient has a fever of at least 38° C. on initiating treatment. 
     
     
         33 - 35 . (canceled) 
     
     
         36 . The method of  claim 32 , wherein a peptide having an amino acid sequence comprising KLSSIETDV (SEQ ID NO:10) is administered. 
     
     
         37 . The method of  claim 36 , wherein a peptide having an amino acid sequence comprising YGRKKRRQRRRKLSSIETDV (SEQ ID NO:11) is administered. 
     
     
         38 . The method of  claim 36 , wherein a peptide having an amino acid sequence consisting of YGRKKRRQRRRKLSSIETDV (SEQ ID NO:11) is administered. 
     
     
         39 . The method of  claim 32 , wherein a peptide having an amino acid sequence comprising KLSSIESDV (SEQ ID NO:9) is administered. 
     
     
         40 . The method of  claim 32 , wherein a peptide having an amino acid sequence comprising YGRKKRRQRRRKLSSIESDV (SEQ ID NO:12) is administered. 
     
     
         41 . The method of  claim 40 , wherein a peptide having an amino acid sequence comprising YGRKKRRQRRRKLSSIESDV (SEQ ID NO:12) is administered. 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 32 , wherein the patient has stroke exacerbated by a fever of at least 39° C. degrees for a period within 6-24 hours after onset of stroke. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The method of  claim 32 , wherein the patient has stroke exacerbated by a fever of at least 40° C. at least for a period between 6-24 hours after onset of stroke. 
     
     
         47 . The method of  claim 32 , wherein the fever is due to concurrent infection. 
     
     
         48 . The method of  claim 32 , wherein the fever is due to location of the stroke in a region of the brain affecting body temperature regulation or set-point. 
     
     
         49 . The method of  claim 32 , wherein the subject is also suffering from hyperglycemia substantially concurrent with onset of stroke. 
     
     
         50 . The method of  claim 49 , wherein the hyperglycemia is due to diabetes. 
     
     
         51 . The method of  claim 32 , wherein the stroke is an ischemic stroke. 
     
     
         52 . The method of  claim 32 , wherein the method reduces the infarction volume resulting from the stroke by at least 15%. 
     
     
         53 - 92 . (canceled)