Abstract
AbstractProgress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8–2.5 fold increase in clusterin mRNA expression in lesioned brain areas in rats with lateral fluid-percussion injury (FPI)-induced TBI. On this basis, we hypothesized that TBI leads to increases in the brain levels of clusterin protein, and consequently, increased plasma clusterin levels. For evaluation, we induced TBI in adult male Sprague-Dawley rats (n = 80) by lateral FPI. We validated our mRNA-seq findings with RT-qPCR, confirming increased clusterin mRNA levels in the perilesional cortex (FC 3.3, p < 0.01) and ipsilateral thalamus (FC 2.4, p < 0.05) at 3 months post-TBI. Immunohistochemistry revealed a marked increase in extracellular clusterin protein expression in the perilesional cortex and ipsilateral hippocampus (7d to 1 month post-TBI), and ipsilateral thalamus (14d to 12 months post-TBI). In the thalamus, punctate immunoreactivity was most intense around activated microglia and mitochondria. Enzyme-linked immunoassays indicated that an acute 15% reduction, rather than an increase in plasma clusterin levels differentiated animals with TBI from sham-operated controls (AUC 0.851, p < 0.05). Our findings suggest that plasma clusterin is a candidate biomarker for acute TBI diagnosis.
Publisher
Springer Science and Business Media LLC
Reference60 articles.
1. Dewan, M. C. et al. Estimating the global incidence of traumatic brain injury. J. Neurosurg. 130, 1–18 (2018).
2. Roozenbeek, B., Maas, A. I. R. & Menon, D. K. Changing patterns in the epidemiology of traumatic brain injury. Nat. Rev. Neurol. 9, 231–6 (2013).
3. Peeters, W. et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir. (Wien). 157, 1683–1696 (2015).
4. Corrigan, J. D., Selassie, A. W. & Orman, J. A. (Langlois). The Epidemiology of Traumatic Brain Injury. J. Head Trauma Rehabil. 25 (2010).
5. Narayan, R. K. et al. Clinical trials in head injury. J. Neurotrauma 19, 503–557 (2002).
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献