{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/324"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/324","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Activation of Early Neural Progenitors Is Required for Traumatic Brain Injury-Induced Hippocampal Neurogenesis","abstract":"Traumatic brain injury (TBI) is the most common form of acquired brain injury in both children and adults in the United States. TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus-dependent functions. However, cognitive recovery commonly occurs though the mechanism is unknown. Exploration of post-natal neurogenesis in the hippocampus raises the possibility that adult-born neurons may contribute to cognitive recovery from TBI. Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult-born neurons in the dentate gyrus and those adult-born neurons may correlate with cognitive recovery. Due to the limits of current methodology in studying neurogenesis, it remains unclear what relevance injury-induced neurogenesis may have in the recovery process following TBI. In order to explore the relevance of injury-induced neurogenesis, I have characterized a previously generated transgenic mouse line that has rtTA-IRES-eGFP expression under the control of a nestin promoter and also contains a neural progenitor-specific regulatory element. By using this line, I have demonstrated that eGFP-expressing cells represent early neural progenitors in the adult dentate gyrus. Performing unilateral controlled cortical injury (CCI) demonstrates that this injury depletes doublecoritn (Dcx)-expressing late neural progenitors while activating eGFP-expressing early neural progenitors. To address whether the subsequent recovery of Dcx-expressing late progenitors was derived from activation of early neural progenitors, I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta-HSV-TK) under the control of the neural progenitor-specific regulatory element of the nestin gene. This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir. Using this line, I demonstrate that ablation of dividing GFP-expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir. CCI on these mice, reveals that no newly born Dcx-expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir. However, the repopulation of Dcx-expressing cells is apparent when ganciclovir was removed one day before injury. Four weeks after injury, those newly born Dcx-expressing cells became mature NeuN-expressing neurons. This suggests that injury-induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons.","abstract_html":"Traumatic brain injury (TBI) is the most common form of acquired brain injury in both children and adults in the United States. TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus-dependent functions. However, cognitive recovery commonly occurs though the mechanism is unknown. Exploration of post-natal neurogenesis in the hippocampus raises the possibility that adult-born neurons may contribute to cognitive recovery from TBI. Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult-born neurons in the dentate gyrus and those adult-born neurons may correlate with cognitive recovery. Due to the limits of current methodology in studying neurogenesis, it remains unclear what relevance injury-induced neurogenesis may have in the recovery process following TBI. In order to explore the relevance of injury-induced neurogenesis, I have characterized a previously generated transgenic mouse line that has rtTA-IRES-eGFP expression under the control of a nestin promoter and also contains a neural progenitor-specific regulatory element. By using this line, I have demonstrated that eGFP-expressing cells represent early neural progenitors in the adult dentate gyrus. Performing unilateral controlled cortical injury (CCI) demonstrates that this injury depletes doublecoritn (Dcx)-expressing late neural progenitors while activating eGFP-expressing early neural progenitors. To address whether the subsequent recovery of Dcx-expressing late progenitors was derived from activation of early neural progenitors, I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta-HSV-TK) under the control of the neural progenitor-specific regulatory element of the nestin gene. This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir. Using this line, I demonstrate that ablation of dividing GFP-expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir. CCI on these mice, reveals that no newly born Dcx-expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir. However, the repopulation of Dcx-expressing cells is apparent when ganciclovir was removed one day before injury. Four weeks after injury, those newly born Dcx-expressing cells became mature NeuN-expressing neurons. This suggests that injury-induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons.","abstract_has_math":false,"creators":["Yu, Tzong-Shiue"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Kernie, Steven G."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T17:35:33Z","date_published":"2010-07-12T17:35:33Z","updated_at":"2026-07-24T05:52:15Z","subjects":["Brain Injuries","Neurogenesis","Stem Cells"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["759166388"],"render_values":[{"text":"759166388","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/324","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kernie, Steven G."]},{"key":"dc:creator","label":"Author","values":["Yu, Tzong-Shiue"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07-12T17:35:33Z","2008-09-19"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text","dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Brain Injuries","Neurogenesis","Stem Cells"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/324","759166388"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Traumatic brain injury (TBI) is the most common form of acquired brain injury in both children and adults in the United States. TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus-dependent functions. However, cognitive recovery commonly occurs though the mechanism is unknown. Exploration of post-natal neurogenesis in the hippocampus raises the possibility that adult-born neurons may contribute to cognitive recovery from TBI. Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult-born neurons in the dentate gyrus and those adult-born neurons may correlate with cognitive recovery. Due to the limits of current methodology in studying neurogenesis, it remains unclear what relevance injury-induced neurogenesis may have in the recovery process following TBI. In order to explore the relevance of injury-induced neurogenesis, I have characterized a previously generated transgenic mouse line that has rtTA-IRES-eGFP expression under the control of a nestin promoter and also contains a neural progenitor-specific regulatory element. By using this line, I have demonstrated that eGFP-expressing cells represent early neural progenitors in the adult dentate gyrus. Performing unilateral controlled cortical injury (CCI) demonstrates that this injury depletes doublecoritn (Dcx)-expressing late neural progenitors while activating eGFP-expressing early neural progenitors. To address whether the subsequent recovery of Dcx-expressing late progenitors was derived from activation of early neural progenitors, I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta-HSV-TK) under the control of the neural progenitor-specific regulatory element of the nestin gene. This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir. Using this line, I demonstrate that ablation of dividing GFP-expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir. CCI on these mice, reveals that no newly born Dcx-expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir. However, the repopulation of Dcx-expressing cells is apparent when ganciclovir was removed one day before injury. Four weeks after injury, those newly born Dcx-expressing cells became mature NeuN-expressing neurons. This suggests that injury-induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Activation of Early Neural Progenitors Is Required for Traumatic Brain Injury-Induced Hippocampal Neurogenesis"]}]}],"canonical_facts":{"dc:contributor":["Kernie, Steven G."],"dc:creator":["Yu, Tzong-Shiue"],"dc:date":["2010-07-12T17:35:33Z","2008-09-19"],"dc:description":["Traumatic brain injury (TBI) is the most common form of acquired brain injury in both children and adults in the United States. TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus-dependent functions. However, cognitive recovery commonly occurs though the mechanism is unknown. Exploration of post-natal neurogenesis in the hippocampus raises the possibility that adult-born neurons may contribute to cognitive recovery from TBI. Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult-born neurons in the dentate gyrus and those adult-born neurons may correlate with cognitive recovery. Due to the limits of current methodology in studying neurogenesis, it remains unclear what relevance injury-induced neurogenesis may have in the recovery process following TBI. In order to explore the relevance of injury-induced neurogenesis, I have characterized a previously generated transgenic mouse line that has rtTA-IRES-eGFP expression under the control of a nestin promoter and also contains a neural progenitor-specific regulatory element. By using this line, I have demonstrated that eGFP-expressing cells represent early neural progenitors in the adult dentate gyrus. Performing unilateral controlled cortical injury (CCI) demonstrates that this injury depletes doublecoritn (Dcx)-expressing late neural progenitors while activating eGFP-expressing early neural progenitors. To address whether the subsequent recovery of Dcx-expressing late progenitors was derived from activation of early neural progenitors, I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta-HSV-TK) under the control of the neural progenitor-specific regulatory element of the nestin gene. This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir. Using this line, I demonstrate that ablation of dividing GFP-expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir. CCI on these mice, reveals that no newly born Dcx-expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir. However, the repopulation of Dcx-expressing cells is apparent when ganciclovir was removed one day before injury. Four weeks after injury, those newly born Dcx-expressing cells became mature NeuN-expressing neurons. This suggests that injury-induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/324","759166388"],"dc:language":["en"],"dc:subject":["Brain Injuries","Neurogenesis","Stem Cells"],"dc:title":["Activation of Early Neural Progenitors Is Required for Traumatic Brain Injury-Induced Hippocampal Neurogenesis"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:15Z"}