Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.

IF 1.8 Q3 CLINICAL NEUROLOGY Neurotrauma reports Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI:10.1089/neur.2024.0060
Lulin Li, Andy Nguyen, Brian Zhao, Ryan Vest, Lakshmi Yerra, Bryan Sun, Jian Luo
{"title":"Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.","authors":"Lulin Li, Andy Nguyen, Brian Zhao, Ryan Vest, Lakshmi Yerra, Bryan Sun, Jian Luo","doi":"10.1089/neur.2024.0060","DOIUrl":null,"url":null,"abstract":"<p><p>Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1016-1026"},"PeriodicalIF":1.8000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499285/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotrauma reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/neur.2024.0060","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
小分子药物 C381 可减轻重复性轻度创伤后的脑血管损伤
创伤性脑损伤(TBI)仍然是一个重大的公共卫生问题,目前还没有有效的治疗干预措施来改善其持久的后果。对创伤性脑损伤病理生理学的普遍认识表明,血管功能障碍起着核心作用。转化生长因子-β(TGF-β)是一种对血管发育至关重要的多功能细胞因子。TGF-β信号传导异常与多种神经系统疾病相关的血管病变有关。我们最近开发了一种新型小分子药物 C381,它是一种 TGF-β 激活剂,具有恢复溶酶体功能的能力。在这里,我们使用重复性轻度创伤性脑损伤(mTBI)小鼠模型来研究 C381 是否能减轻血管损伤。我们首先采用 RNA-seq 分析方法研究了与 mTBI 相关的基因表达模式,并评估了 C381 在减轻这些变化方面的治疗潜力。我们的研究结果表明,与 mTBI 相关的基因表达特征各不相同,主要涉及与血管完整性和内皮功能相关的通路。值得注意的是,用 C381 治疗可逆转这些 mTBI 诱导的基因表达变化。免疫组化分析进一步证实了这些发现,显示 C381 治疗减轻了受 mTBI 影响的脑组织中的血管损伤。这些研究结果有力地支持了 C381 作为一种新型治疗干预手段对 mTBI 的潜在临床实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
2.40
自引率
0.00%
发文量
0
审稿时长
8 weeks
期刊最新文献
Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury. Clinical Impact of an AI Decision Support System for Detection of Intracranial Hemorrhage in CT Scans. Metacognitive Therapy for People Experiencing Persistent Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Preliminary Multiple Case-Series Study. Multicenter Study Examining Temporal Trends in Traumatic Intracranial Hemorrhage Over Six Years Using Joinpoint Regression. Resilience and Concussion Recovery in Minority Women: Promoting Health Equity.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1