Compositions and methods for enhancing neuro-repair

Abstract

The present invention relates to methods for enhancing recovery after an ischemic injury, including cerebral ischemia and stroke, by administration of therapeutic amounts of Domain V protein.

1 . A method of enhancing neurogenic neurorepair in a subject in need comprising:
 administering Perlecan Domain V (DV) or DV fragment to the subject, wherein administration of DV or DV fragment increases the number of new post-ischemic event mature neurons in an area of the brain of the subject damaged by the ischemic event.   
     
     
         2 . The method of  claim 1 , wherein the subject has had a traumatic brain injury or stroke. 
     
     
         3 . The method of  claim 2 , wherein DV or DV fragment is first administered to the subject more than 24 hours after the traumatic brain injury or stroke to increase neurogenesis. 
     
     
         4 . The method of  claim 1 , wherein the DV fragment is LG3. 
     
     
         5 . The method of  claim 1 , wherein the administering occurs daily for a period of 1 day to two weeks. 
     
     
         6 . The method of  claim 1 , wherein the administering step includes administering about 0.5 mg/kg to about 20 mg/kg of the DV. 
     
     
         7 . The method of  claim 1 , wherein neural precursor cells and/or peri-infarct neurite density is increased. 
     
     
         8 . The method of  claim 1 , wherein administering the DV includes administering the DV intravenously or administering the DV intraperitoneally. 
     
     
         9 . The method of  claim 1 , wherein the administering increases neurogenesis, increases neuron survival, improves functional recovery, improves motor function, increases outgrowth of new neurons, restores excitatory synaptic transmission, reverses ischemic induced changes to excitatory post synaptic currents, increases neurosphere expansion, and/or increases neuroblast migration compared to a control subject that does not receive DV. 
     
     
         10 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         11 . The method of  claim 10 , wherein the subject is a mouse or a human.