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