A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice
Abstract Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-024-03014-w |
| _version_ | 1797355679928811520 |
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| author | Tamara L. Baker David K. Wright Alessandro D. Uboldi Christopher J. Tonkin Anh Vo Trevor Wilson Stuart J. McDonald Richelle Mychasiuk Bridgette D. Semple Mujun Sun Sandy R. Shultz |
| author_facet | Tamara L. Baker David K. Wright Alessandro D. Uboldi Christopher J. Tonkin Anh Vo Trevor Wilson Stuart J. McDonald Richelle Mychasiuk Bridgette D. Semple Mujun Sun Sandy R. Shultz |
| author_sort | Tamara L. Baker |
| collection | DOAJ |
| description | Abstract Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity—all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients. |
| first_indexed | 2024-03-08T14:14:35Z |
| format | Article |
| id | doaj.art-dd19e4fc213b4406a1fdbe90f4f928eb |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-08T14:14:35Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-dd19e4fc213b4406a1fdbe90f4f928eb2024-01-14T12:30:43ZengBMCJournal of Neuroinflammation1742-20942024-01-0121113110.1186/s12974-024-03014-wA pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in miceTamara L. Baker0David K. Wright1Alessandro D. Uboldi2Christopher J. Tonkin3Anh Vo4Trevor Wilson5Stuart J. McDonald6Richelle Mychasiuk7Bridgette D. Semple8Mujun Sun9Sandy R. Shultz10Department of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDivision of Infectious Disease and Immune Defense, , The Walter and Eliza Hall Institute of Medical ResearchDivision of Infectious Disease and Immune Defense, , The Walter and Eliza Hall Institute of Medical ResearchMonash Health Translation Precinct, Monash UniversityMonash Health Translation Precinct, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityAbstract Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity—all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.https://doi.org/10.1186/s12974-024-03014-wNeuroinflammationImmune responseOxidative stressExcitotoxicityFemalesSex |
| spellingShingle | Tamara L. Baker David K. Wright Alessandro D. Uboldi Christopher J. Tonkin Anh Vo Trevor Wilson Stuart J. McDonald Richelle Mychasiuk Bridgette D. Semple Mujun Sun Sandy R. Shultz A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice Journal of Neuroinflammation Neuroinflammation Immune response Oxidative stress Excitotoxicity Females Sex |
| title | A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| title_full | A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| title_fullStr | A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| title_full_unstemmed | A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| title_short | A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| title_sort | pre existing toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice |
| topic | Neuroinflammation Immune response Oxidative stress Excitotoxicity Females Sex |
| url | https://doi.org/10.1186/s12974-024-03014-w |
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