期刊
BRAIN RESEARCH BULLETIN
卷 170, 期 -, 页码 1-10出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2021.01.023
关键词
Traumatic brain injury; Hemocoagulase Agkistrodon; Brain-blood barrier; Inflammatory cytokines; Brain edema; Neuroprotection
资金
- National Natural Sciences Foundation of China [81872855, 81673420]
- CAMS Innovation Fund for Medical Sciences [2017-I2M-2-004]
- National Science and Technology Major Special Project on Major New Drug Innovation of China [2018ZX09711001-003-005, 2018ZX09711001-003-009]
- National Key R&D Program of China [2019YFC1708901]
- Fundamental Research Funds for the Central Universities of China [3332019070]
- Disciplines construction project of China [20190200802]
The study revealed that Hemocoagulase Agkistrodon (HCA) has neuroprotective effects in experimental traumatic brain injury (TBI), improving neurological deficits, reducing brain edema and hemorrhage, lowering proinflammatory cytokines while increasing anti-inflammatory cytokine levels, and diminishing BBB disruption by regulating tight junction proteins. These findings suggest the therapeutic potential of HCA in acute TBI to mitigate neuropathological damage.
Traumatic brain injury (TBI) is the major cause of disability and mortality among young people and is associated with neurodegenerative diseases. However, the available clinical options have limited effectiveness. Here, we investigated the neuroprotective effect of Hemocoagulase Agkistrodon (HCA), a thrombin-like enzyme (TLE) isolated and purified from snake venom. Rats subjected to experimental TBI were administered a single dose of HCA or vehicle 10 min after injury. Neurological function was assessed with modified neurological severity score (mNSS). Brain edema were evaluated by measuring brain water content. Levels of hemoglobin and inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA). In addition, assays including Evans blue extravasation, Western blot analysis and immunofluorescence staining were utilized to determined blood-brain barrier (BBB) integrity. Our results showed that HCA treatment ameliorated neurological deficits (p < 0.01), alleviated brain edema (p < 0.01) and hemorrhage (p < 0.01), decreased the production of the proinflammatory cytokines IL-1 beta (p < 0.01), TNF-alpha (p < 0.01) and IL-6 (p < 0.05), and increased the anti- inflammatory cytokine IL-10 at the contusion site (p < 0.01). Moreover, HCA administration reduced BBB disruption by regulating expression of tight junction proteins, including ZO-1, occludin and claudin-5 (ps < 0.01). Together, our results demonstrate that HCA might have therapeutic efficacy in acute TBI, suggesting a potential clinical application for mitigating the neuropathological damage associated with TBI.
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