{"id":{"repo_id":"gmu","oai_identifier":"oai:MARS:1920/15250"},"canonical_url":"https://search.dev.ndltd.org/etd/gmu/oai:MARS:1920/15250","repository":{"repo_id":"gmu","name":"George Mason University","base_url":"https://mars.gmu.edu/server/oai/request"},"display":{"title":"Effects of Isoflurane Exposure on Spatial Memory Performance and Neuronal Density in Mice: Evaluating a Potential Confound","abstract":"Mild traumatic brain injury, a form of traumatic brain injury (TBI) accounting for over 1 million of the reported TBI’s annually in the United States, is underreported in literature because of the transient effects and lack of targeted treatments. Although a single mild TBI may resolve easily without treatment, repeated mild traumatic brain injury (rmTBI) can prolong recovery time and increase the risk of long-term neurodegeneration. To investigate these effects, animal models have been developed to replicate rmTBI, with a vast majority of those techniques relying on the use of anesthetization in the form of isoflurane while administering each TBI to minimize pain and suffering. The administration of anesthetic, however, has been associated with many of the same behavioral and morphological effects observed from rmTBI administration, including neuronal death and spatial memory deficits, potentially confounding scientific outcomes. To assess whether isoflurane exposure influences rmTBI research findings in mice, two studies were conducted. Study 1 used a machine learning pipeline (DeepLabCut and a multilayer perceptron network) to classify swim strategies in the Morris Water Maze (MWM) among anesthetized groups and a non-anesthetized control group. Analyses revealed a significant effect of Day in all variables measured (Cognitive Score, Time to Platform, Distance Travelled), but also that in Distance Travelled, Control mice travelled significantly longer distances, without spending more time finding the platform, suggesting increased activity when compared to other groups. Study 2 investigated EZM, OF, Wirehang, Rotarod and neuronal density among anesthetized groups and a non-anesthetized control group in 6 brain regions (CA1, CA3, PAC, IL, EC) using cresyl-violet staining. The behavioral analyses suggest that Control mice exhibited higher anxiety-like behavior in both OF and EZM in the immediate timeframe, but that those effects disappear in the delayed timeframe, suggesting isoflurane exposure may have a short-term effect on anxiety-like behavior in mice. Morphological analyses revealed no significant group differences in any of the brain regions analyzed other than the EC, where a trend was observed in which TBI Saline mice had higher cell density than Sham Saline, suggesting that TBI may have had a positive impact on the cell density in the EC, rather than a detrimental effect. These results suggest that repeated isoflurane exposure may have a short-term confounding effect on anxiety-like behavior in mice, but within 2 months the effects converge and are no longer distinguishable between groups. However, the lack of observable differences between rmTBI and sham mouse groups in many of the analyses highlights limitations in the injury model itself. Future research should be performed to better understand the relationships between rmTBI, anesthetization, behavior, and brain morphology, as well as to refine the rmTBI mouse model used in this study.","abstract_html":"Mild traumatic brain injury, a form of traumatic brain injury (TBI) accounting for over 1 million of the reported TBI’s annually in the United States, is underreported in literature because of the transient effects and lack of targeted treatments. Although a single mild TBI may resolve easily without treatment, repeated mild traumatic brain injury (rmTBI) can prolong recovery time and increase the risk of long-term neurodegeneration. To investigate these effects, animal models have been developed to replicate rmTBI, with a vast majority of those techniques relying on the use of anesthetization in the form of isoflurane while administering each TBI to minimize pain and suffering. The administration of anesthetic, however, has been associated with many of the same behavioral and morphological effects observed from rmTBI administration, including neuronal death and spatial memory deficits, potentially confounding scientific outcomes. To assess whether isoflurane exposure influences rmTBI research findings in mice, two studies were conducted. Study 1 used a machine learning pipeline (DeepLabCut and a multilayer perceptron network) to classify swim strategies in the Morris Water Maze (MWM) among anesthetized groups and a non-anesthetized control group. Analyses revealed a significant effect of Day in all variables measured (Cognitive Score, Time to Platform, Distance Travelled), but also that in Distance Travelled, Control mice travelled significantly longer distances, without spending more time finding the platform, suggesting increased activity when compared to other groups. Study 2 investigated EZM, OF, Wirehang, Rotarod and neuronal density among anesthetized groups and a non-anesthetized control group in 6 brain regions (CA1, CA3, PAC, IL, EC) using cresyl-violet staining. The behavioral analyses suggest that Control mice exhibited higher anxiety-like behavior in both OF and EZM in the immediate timeframe, but that those effects disappear in the delayed timeframe, suggesting isoflurane exposure may have a short-term effect on anxiety-like behavior in mice. Morphological analyses revealed no significant group differences in any of the brain regions analyzed other than the EC, where a trend was observed in which TBI Saline mice had higher cell density than Sham Saline, suggesting that TBI may have had a positive impact on the cell density in the EC, rather than a detrimental effect. These results suggest that repeated isoflurane exposure may have a short-term confounding effect on anxiety-like behavior in mice, but within 2 months the effects converge and are no longer distinguishable between groups. However, the lack of observable differences between rmTBI and sham mouse groups in many of the analyses highlights limitations in the injury model itself. Future research should be performed to better understand the relationships between rmTBI, anesthetization, behavior, and brain morphology, as well as to refine the rmTBI mouse model used in this study.","abstract_has_math":false,"creators":["Neff, Samuel Lock"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-27T19:51:54Z","subjects":["Anesthesia","Isoflurane","Neurodegeneration","rmTBI","Traumatic Brain Injury","Young Blood"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/15250"],"render_values":[{"text":"hdl:1920/15250","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Anesthesia","Isoflurane","Neurodegeneration","rmTBI","Traumatic Brain Injury","Young Blood"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/15250"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["Mild traumatic brain injury, a form of traumatic brain injury (TBI) accounting for over 1 million of the reported TBI’s annually in the United States, is underreported in literature because of the transient effects and lack of targeted treatments. Although a single mild TBI may resolve easily without treatment, repeated mild traumatic brain injury (rmTBI) can prolong recovery time and increase the risk of long-term neurodegeneration. To investigate these effects, animal models have been developed to replicate rmTBI, with a vast majority of those techniques relying on the use of anesthetization in the form of isoflurane while administering each TBI to minimize pain and suffering. The administration of anesthetic, however, has been associated with many of the same behavioral and morphological effects observed from rmTBI administration, including neuronal death and spatial memory deficits, potentially confounding scientific outcomes. To assess whether isoflurane exposure influences rmTBI research findings in mice, two studies were conducted. Study 1 used a machine learning pipeline (DeepLabCut and a multilayer perceptron network) to classify swim strategies in the Morris Water Maze (MWM) among anesthetized groups and a non-anesthetized control group. Analyses revealed a significant effect of Day in all variables measured (Cognitive Score, Time to Platform, Distance Travelled), but also that in Distance Travelled, Control mice travelled significantly longer distances, without spending more time finding the platform, suggesting increased activity when compared to other groups. Study 2 investigated EZM, OF, Wirehang, Rotarod and neuronal density among anesthetized groups and a non-anesthetized control group in 6 brain regions (CA1, CA3, PAC, IL, EC) using cresyl-violet staining. The behavioral analyses suggest that Control mice exhibited higher anxiety-like behavior in both OF and EZM in the immediate timeframe, but that those effects disappear in the delayed timeframe, suggesting isoflurane exposure may have a short-term effect on anxiety-like behavior in mice. Morphological analyses revealed no significant group differences in any of the brain regions analyzed other than the EC, where a trend was observed in which TBI Saline mice had higher cell density than Sham Saline, suggesting that TBI may have had a positive impact on the cell density in the EC, rather than a detrimental effect. These results suggest that repeated isoflurane exposure may have a short-term confounding effect on anxiety-like behavior in mice, but within 2 months the effects converge and are no longer distinguishable between groups. However, the lack of observable differences between rmTBI and sham mouse groups in many of the analyses highlights limitations in the injury model itself. Future research should be performed to better understand the relationships between rmTBI, anesthetization, behavior, and brain morphology, as well as to refine the rmTBI mouse model used in this study."]},{"key":"dc:title","label":"Title","values":["Effects of Isoflurane Exposure on Spatial Memory Performance and Neuronal Density in Mice: Evaluating a Potential Confound"]}]}],"canonical_facts":{"dc:date.issued":["2025"],"dc:description.other":["Mild traumatic brain injury, a form of traumatic brain injury (TBI) accounting for over 1 million of the reported TBI’s annually in the United States, is underreported in literature because of the transient effects and lack of targeted treatments. Although a single mild TBI may resolve easily without treatment, repeated mild traumatic brain injury (rmTBI) can prolong recovery time and increase the risk of long-term neurodegeneration. To investigate these effects, animal models have been developed to replicate rmTBI, with a vast majority of those techniques relying on the use of anesthetization in the form of isoflurane while administering each TBI to minimize pain and suffering. The administration of anesthetic, however, has been associated with many of the same behavioral and morphological effects observed from rmTBI administration, including neuronal death and spatial memory deficits, potentially confounding scientific outcomes. To assess whether isoflurane exposure influences rmTBI research findings in mice, two studies were conducted. Study 1 used a machine learning pipeline (DeepLabCut and a multilayer perceptron network) to classify swim strategies in the Morris Water Maze (MWM) among anesthetized groups and a non-anesthetized control group. Analyses revealed a significant effect of Day in all variables measured (Cognitive Score, Time to Platform, Distance Travelled), but also that in Distance Travelled, Control mice travelled significantly longer distances, without spending more time finding the platform, suggesting increased activity when compared to other groups. Study 2 investigated EZM, OF, Wirehang, Rotarod and neuronal density among anesthetized groups and a non-anesthetized control group in 6 brain regions (CA1, CA3, PAC, IL, EC) using cresyl-violet staining. The behavioral analyses suggest that Control mice exhibited higher anxiety-like behavior in both OF and EZM in the immediate timeframe, but that those effects disappear in the delayed timeframe, suggesting isoflurane exposure may have a short-term effect on anxiety-like behavior in mice. Morphological analyses revealed no significant group differences in any of the brain regions analyzed other than the EC, where a trend was observed in which TBI Saline mice had higher cell density than Sham Saline, suggesting that TBI may have had a positive impact on the cell density in the EC, rather than a detrimental effect. These results suggest that repeated isoflurane exposure may have a short-term confounding effect on anxiety-like behavior in mice, but within 2 months the effects converge and are no longer distinguishable between groups. However, the lack of observable differences between rmTBI and sham mouse groups in many of the analyses highlights limitations in the injury model itself. Future research should be performed to better understand the relationships between rmTBI, anesthetization, behavior, and brain morphology, as well as to refine the rmTBI mouse model used in this study."],"dc:identifier":["hdl:1920/15250"],"dc:subject":["Anesthesia","Isoflurane","Neurodegeneration","rmTBI","Traumatic Brain Injury","Young Blood"],"dc:title":["Effects of Isoflurane Exposure on Spatial Memory Performance and Neuronal Density in Mice: Evaluating a Potential Confound"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T19:51:54Z"}