Animal model of neuronal injury

Abstract

The present invention provides non-human animal models of neuronal injury and/or cognitive dysfunction and methods of making and using such animal models. The animal models of the invention are particularly suited to assessing neurodegeneration in selected regions of interest in the CNS, and thus especially useful for testing the therapeutic efficacy of agents targeting neurodegeneration associated with aging, neurodegenerative diseases, autoimmunity and trauma (e.g., ischemia).

1 . A method of inducing neuronal injury in a region of interest in a non-human animal comprising:
 introducing a fibrinogen agent to one or more regions of the animal's central nervous system (CNS),   wherein said fibrinogen agent induces neuronal injury associated with microglial activation in the CNS.   
     
     
         2 . The method of  claim 1 , wherein administration of a fibrinogen agent results in a decrease in dendritic spine density. 
     
     
         3 . The method of  claim 1 , wherein the fibrinogen agent is administered to one or more regions of the brain. 
     
     
         4 . The method of  claim 3 , wherein the region of interest is the dentate gyrus, substantia nigra, cortex or corpus callosum. 
     
     
         5 . The method of  claim 1 , wherein the animal exhibits cognitive impairment resulting from the neuronal injury. 
     
     
         6 . The method of  claim 1 , wherein the fibrinogen agent is administered to the spinal cord. 
     
     
         7 . The method of  claim 1 , wherein the induced neuronal injury is localized neuronal injury. 
     
     
         8 . The method of  claim 1 , wherein the animal further comprises one or more genetic traits associated with an increased risk of neurodegenerative disease. 
     
     
         9 . The method of  claim 1 , wherein the fibrinogen agent is full-length fibrinogen. 
     
     
         10 . The method of  claim 1 , wherein the fibrinogen agent is a biologically active fragment of fibrinogen. 
     
     
         11 . The method of  claim 1 , wherein the fibrinogen agent is labeled. 
     
     
         12 . A method of creating a non-human animal model of demyelination, comprising
 introducing a fibrinogen agent to one or more regions of the animal's central nervous system (CNS),   wherein said fibrinogen agent induces demyelination in the one or more regions of the of the CNS of the animal.   
     
     
         13 . The method of  claim 12 , wherein the fibrinogen agent is administered into one or more regions of the brain. 
     
     
         14 . The method of  claim 13 , wherein the region of interest is the dentate gyrus, substantia nigra, cortex or corpus callosum. 
     
     
         15 . The method of  claim 12 , wherein the animal exhibits cognitive impairment resulting from the administration of the fibrinogen agent. 
     
     
         16 . The method of  claim 12 , wherein the fibrinogen agent is administered to the spinal cord. 
     
     
         17 . The method of  claim 12 , wherein the induced neuronal injury is localized neuronal injury. 
     
     
         18 . The method of  claim 12 , wherein the animal further comprises one or more genetic traits associated with an increased risk of neurodegenerative disease. 
     
     
         19 . The method of  claim 12 , wherein the fibrinogen agent is full-length fibrinogen. 
     
     
         20 . The method of  claim 12 , wherein the fibrinogen agent is a biologically active fragment of fibrinogen. 
     
     
         21 . The method of  claim 1 , wherein the fibrinogen agent is labeled. 
     
     
         22 . The method of  claim 1 , wherein the fibrinogen agent is labeled.