Neuroinflammation has been linked to the pathogenesis of many diseases, including chronic traumatic encephalopathy (CTE). CTE is a progressive neurodegenerative disease caused by exposure to repeated head impacts (RHI) from a variety of sources, including contact sports and military injury. CTE is characterized neuropathologically by the deposition of hyperphosphorylated tau (p-tau) in neurons as neurofibrillary tangles (NFT) and neurites at the depths of the cortical sulci in an irregular pattern. In addition to p-tau accumulation, there is also an accumulation of pigment-containing macrophages around small blood vessels in the white matter and widespread microglial inflammation in CTE. Macrophage and microglial inflammation can be beneficial to tissue repair, but if persistent, can precipitate neurodegeneration. This study quantified the density of perivascular CD68+ macrophages in the dorsolateral prefrontal (DLF) white matter, a brain region known to be affected early in CTE in post-mortem brain tissue from 46 individuals, 7 controls (mean age: 46.14, SD: 11.39, range: 22-55), 20 individuals exposed to RHI without CTE (mean age: 22.75, SD: 3.65, range: 17- 29), and 19 individuals, all of them American football players, with pathologically verified CTE (mean age: 25.11, SD: 2.92, range: 18-29). Brain tissue was provided by the Injury and Traumatic Encephalopathy (UNITE) brain bank and the post-traumatic stress disorder (PTSD) brain bank. Comparisons were made between controls, individuals exposed to RHI without CTE, and individuals with CTE. Fixed tissue samples of the DLF cortex and white matter were cut at 10μm and stained with CD68 to mark perivascular macrophages. Slides were imaged with a brightfield microscope at 40x magnification and analyzed using the HALO image software analysis platform. In the total population, a one-way test of variance (ANOVA) revealed a statistically significant increase in perivascular macrophages, indicated by CD68 positive pixels, in Stage III CTE compared to controls (p<0.05), a significant increase in Stage II compared to Stage I CTE (p<0.05), and a statistically significant increase in Stage III compared to Stage I CTE (p<0.01). The analysis also revealed a trend toward more CD68 pixels in Stage II CTE compared to controls (p=0.0883) and a trend toward more pixels in Stage III CTE compared to RHI no CTE (p=0.0705). Among the American football players, analyses revealed that Stage II CTE had significantly more perivascular macrophages than Stage I CTE (p<0.01), Stage II CTE had significantly more than controls (p<0.01), Stage III CTE had significantly more than Stage I CTE (p<0.05), and Stage III CTE had significantly more than controls (p<0.05). In summary, this study demonstrates that there is an increase in perivascular CD68 positive macrophages in individuals exposed to RHI with and without CTE. Perivascular macrophages and other neuroinflammatory molecules may play a critical role in the pathogenesis of CTE.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48274 |
| Date | 28 February 2024 |
| Creators | Johnsgard, Kristen Nicole |
| Contributors | McKee, Ann, Cherry, Jonathan |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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