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在大鼠创伤性脑损伤模型中,使用单一脑样本中的低和高分子量复合物评估血脑屏障破坏:与一种已建立的磁共振成像技术的比较。

Evaluation of Blood-Brain Barrier Disruption Using Low- and High-Molecular-Weight Complexes in a Single Brain Sample in a Rat Traumatic Brain Injury Model: Comparison to an Established Magnetic Resonance Imaging Technique.

机构信息

Department of Radiology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.

出版信息

Int J Mol Sci. 2024 Oct 19;25(20):11241. doi: 10.3390/ijms252011241.

Abstract

Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood-brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague-Dawley rats were separated into the following five groups: naive rats ( = 20 rats), control rats with administration ( = 20 rats), and TBI rats ( = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method.

摘要

创伤性脑损伤(TBI)是年轻人死亡和残疾的主要原因,给公共卫生和经济带来了重大挑战。尽管 TBI 很常见,但治疗选择仍然在很大程度上不适用。然而,对血脑屏障(BBB)的检查可以帮助我们了解大脑功能障碍的机制和动态,这会对 TBI 患者造成继发性伤害。在这里,我们提出了一个针对 TBI 的大鼠模型,重点关注两个标准的 BBB 评估标志物,即高分子和低分子复合物,以了解 BBB 的破坏情况。此外,我们测试了一种新的技术来评估单个脑组织中的 BBB 破坏情况,并将该新技术与神经影像学进行了比较。总共 100 只 Sprague-Dawley 大鼠被分为以下五组:正常大鼠(=20 只)、给予对照药物的对照大鼠(=20 只)和 TBI 大鼠(=60 只)。大鼠在受伤后不同时间点进行评估,以测量 BBB 破坏情况,使用低分子和高分子复合物。在 TBI 后进行神经学严重程度评分评估。在 TBI 后的神经学检查中,对大鼠进行磁共振成像扫描,然后处死以评估 BBB 通透性。我们发现,这两种标志物在同一组脑组织中在一周的时间内显示出不同的 BBB 破坏情况。我们使用高分子和低分子复合物标志物在单个脑组织中评估 BBB 通透性的创新方案显示出了适当的结果。此外,我们确定了这种方法的较低灵敏度,因此证明了该方法的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12f3/11508800/fc9be626df1d/ijms-25-11241-g001.jpg

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