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The effects of trem2 deficiency On Traumatic brain injury FINAL.pdf (17.87 MB)
ETD Abstract Container
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The Effects of TREM2 deficiency on Traumatic Brain Injury- induced Neuroinflammation and Neurodegeneration
Author Info
Saber, Maha M
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1465648612
Abstract Details
Year and Degree
2016, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Abstract
Traumatic brain injury (TBI) affects 1.7 million people annually in the USA (Center of Disease Control). There is increasing evidence that individuals exposed to TBI have increased risk of developing multiple neurodegenerative conditions, including Alzheimer Disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, infiltration of peripheral monocytes, and the production of cytokines. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating in Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2-/-) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 Days Post Injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency, respectively. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Furthermore, Trem2-/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared to B6 mice exposed to TBI. Flow cytometry also revealed a decrease percentage of peripheral macrophages in the cortexes of Trem2-/- mice exposed to TBI compared to b6 mice exposed to TBI. In addition, at 120 DPI, Trem2-/- mice exposed to TBI demonstrated reduced hippocampal atrophy, and rescue of TBI-induced behavioral changes when compared to B6 mice exposed to TBI. Genetic studies have implicated that there is a dosage effect of TREM2 where homozygous mutations lead to Nasu hakola disease, a dementia coupled with bone cysts, while heterozygous mutations have been shown to correlate with AD. Behavioral studies have been extended to include TREM2 heterozygous mice. TREM2 heterozygous exposed to TBI mice show no TBI induced behavioral changes, similarly to what is seen in Trem2-/- mice. This suggests that TREM2 heterozygousity and deficiency are both neuroprotective against TBI induced behavioral changes. With further studies, these data suggest TREM2 is a potential target for therapeutic treatment for the chronic recovery of TBI patients in ameliorating neurodegenerative-related pathologies.
Committee
Bruce Lamb, PhD (Advisor)
Gary Landreth, PhD (Committee Chair)
Justin Lathia, PhD (Committee Member)
Xiaoxia Li, PhD (Committee Member)
Andrew Russman, DO (Other)
Subject Headings
Neurology
;
Neurosciences
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Citations
Saber, M. M. (2016).
The Effects of TREM2 deficiency on Traumatic Brain Injury- induced Neuroinflammation and Neurodegeneration
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1465648612
APA Style (7th edition)
Saber, Maha.
The Effects of TREM2 deficiency on Traumatic Brain Injury- induced Neuroinflammation and Neurodegeneration.
2016. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1465648612.
MLA Style (8th edition)
Saber, Maha. "The Effects of TREM2 deficiency on Traumatic Brain Injury- induced Neuroinflammation and Neurodegeneration." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1465648612
Chicago Manual of Style (17th edition)
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Document number:
case1465648612
Download Count:
225
Copyright Info
© , all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.