School of Medicine and Health Sciences Poster Presentations
Site-Specific Modulation of the Glial Scar Following Cortical Stab Wound
Poster Number
277
Document Type
Poster
Publication Date
3-2016
Abstract
Reactive astrocytosis and the subsequent glial scar is ubiquitous to injuries of the central nervous system, and primarily serves to protect against further damage, but is also a prominent inhibitor of neuronal regeneration. Manipulating the glial scar following injury has been extensively studied as a means to enhance neuronal regeneration and promote recovery. Previous work has shown that immediate ablation of proliferating astrocytes following injury to the CNS results in leukocyte infiltration and neuronal degeneration. Our work builds on these results, by introducing both spatial and temporal control of astrocyte apoptosis using a mouse model of inducible caspase-9 activity under the mouse GFAP promotor (GFAP-iCP9). Using a cortical stab wound, we tested both immediate and delayed ablation of astrocytes in the vicinity of the injury using chemical inducer of dimerization (CID). Both treatments have resulted in localized ablation of astryctes, but contrary to previous work there was reduced microglial response in both treatment groups. However, only delayed ablation of astrocytes had a protective effect on hippocampal CA1 neurons. Taken together, our results show that an immediate astrocytic response is essential in protecting the injury site, but subsequently serves to limit neuronal survival, partly because of a heightened inflammatory response.
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Open Access
1
Site-Specific Modulation of the Glial Scar Following Cortical Stab Wound
Reactive astrocytosis and the subsequent glial scar is ubiquitous to injuries of the central nervous system, and primarily serves to protect against further damage, but is also a prominent inhibitor of neuronal regeneration. Manipulating the glial scar following injury has been extensively studied as a means to enhance neuronal regeneration and promote recovery. Previous work has shown that immediate ablation of proliferating astrocytes following injury to the CNS results in leukocyte infiltration and neuronal degeneration. Our work builds on these results, by introducing both spatial and temporal control of astrocyte apoptosis using a mouse model of inducible caspase-9 activity under the mouse GFAP promotor (GFAP-iCP9). Using a cortical stab wound, we tested both immediate and delayed ablation of astrocytes in the vicinity of the injury using chemical inducer of dimerization (CID). Both treatments have resulted in localized ablation of astryctes, but contrary to previous work there was reduced microglial response in both treatment groups. However, only delayed ablation of astrocytes had a protective effect on hippocampal CA1 neurons. Taken together, our results show that an immediate astrocytic response is essential in protecting the injury site, but subsequently serves to limit neuronal survival, partly because of a heightened inflammatory response.
Comments
Presented at: GW Research Days 2016