Traumatic brain injury poses a major public health challenge with significant immediate and long-term effects. Repetitive head trauma is an ongoing area of research, and little is known about the response of cerebral blood vessels to such loading. This study investigated the mechanical response of cerebral arteries to repetitive overstretch, hypothesizing that repeated overstretch leads to cumulative damage. To test this hypothesis, middle cerebral artery segments from twelve piglets were subjected to sub-yield, high-rate overstretch of varying severities, with up to 10 repetitions. The stress-stretch behavior of the vessels revealed that repetitive overstretch caused progressive softening that increased with both overstretch magnitude and number of exposures. This softening was notably limited to the toe region, with no changes occurring in the higher-stress, linear portion of the repeated overstretch curves. Mild-to-moderate overstretches resulted in gradual softening, while severe overstretches caused dramatic softening with the first exposure and little further change with subsequent overstretches. Mildly damaged vessels displayed a small amount of recovery with time, but the magnitude of this recovery was minimal and declined with increasing repetitions and severity. No clear relationship was observed between collagen denaturation and the magnitude and number of overstretches. These findings provide important insights into the mechanics of cerebral vessels under repetitive loading, suggesting that vascular damage from repeated trauma accumulates, potentially exacerbating existing injury. These results increase understanding of soft tissue damage and inform the development of constitutive damage models for cerebral arteries, a critical tool needed to improve predictions of traumatic brain injury progression. STATEMENT OF SIGNIFICANCE: This study investigates the mechanical response of cerebral arteries to repetitive overstretch, revealing cumulative softening effects. Unlike previous studies focusing on single overstretch events, our research is the first to explore repetitive exposures in cerebral arteries and to report softening as a function of both overstretch magnitude and number of exposures. Given the role of cerebral vessels in maintaining a healthy brain and their contributions to the structural response of the brain in TBI events, progressive vessel softening in repetitive TBI may lead to increased vulnerability with the potential to exacerbate existing injury. These findings enhance understanding of soft tissue damage mechanisms, providing critical insights for developing constitutive damage models and improving injury predictions in repeated TBI.
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IL-1β Antibody Protects Brain from Neuropathology of Hypoperfusion
Chronic brain hypoperfusion is the primary cause of vascular dementia and has been implicated in the development of white matter disease and lacunar infarcts. Cerebral hypoperfusion leads to a chronic state of brain inflammation with immune cell activation and production of pro-inflammatory cytokines, including IL-1β. In the present study, we induced chronic, progressive brain hypoperfusion in mice using ameroid constrictor, arterial stenosis (ACAS) surgery and tested the efficacy of an IL-1β antibody on the resulting brain damage. We observed that ACAS surgery causes a reduction in cerebral blood flow (CBF) of about 30% and grey and white matter damage in and around the hippocampus. The IL-1β antibody treatment did not significantly affect CBF but largely eliminated grey matter damage and reduced white matter damage caused by ACAS surgery. Over the course of hypoperfusion/injury, grip strength, coordination, and memory-related behavior were not significantly affected by ACAS surgery or antibody treatment. We conclude that antibody neutralization of IL-1β is protective from the brain damage caused by chronic, progressive brain hypoperfusion.
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- Award ID(s):
- 1916894
- PAR ID:
- 10249381
- Date Published:
- Journal Name:
- Cells
- Volume:
- 10
- Issue:
- 4
- ISSN:
- 2073-4409
- Page Range / eLocation ID:
- 855
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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