Frank Dmitry, Gruenbaum Benjamin F, Zvenigorodsky Vladislav, Shelef Ilan, Oleshko Anna, Matalon Frederic, Tsafarov Beatris, Zlotnik Alexander, Frenkel Amit, Boyko Matthew
Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel.
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
Int J Mol Sci. 2024 Apr 11;25(8):4234. doi: 10.3390/ijms25084234.
Traumatic brain injury (TBI) significantly contributes to death and disability worldwide. However, treatment options remain limited. Here, we focus on a specific pathology of TBI, diffuse axonal brain injury (DABI), which describes the process of the tearing of nerve fibers in the brain after blunt injury. Most protocols to study DABI do not incorporate a specific model for that type of pathology, limiting their ability to identify mechanisms and comorbidities of DABI. In this study, we developed a magnetic resonance imaging (MRI) protocol for DABI in a rat model using a 3-T clinical scanner. We compared the neuroimaging outcomes with histologic and neurologic assessments. In a sample size of 10 rats in the sham group and 10 rats in the DABI group, we established neurological severity scores before the intervention and at 48 h following DABI induction. After the neurological evaluation after DABI, all rats underwent MRI scans and were subsequently euthanized for histological evaluation. As expected, the neurological assessment showed a high sensitivity for DABI lesions indicated using the β-APP marker. Surprisingly, however, we found that the MRI method had greater sensitivity in assessing DABI lesions compared to histological methods. Out of the five MRI parameters with pathological changes in the DABI model, we found significant changes compared to sham rats in three parameters, and, as shown using comparative tests with other models, MRI was the most sensitive parameter, being even more sensitive than histology. We anticipate that this DABI protocol will have a significant impact on future TBI and DABI studies, advancing research on treatments specifically targeted towards improving patient quality of life and long-term outcomes.
创伤性脑损伤(TBI)在全球范围内是导致死亡和残疾的重要原因。然而,治疗选择仍然有限。在此,我们聚焦于TBI的一种特定病理情况,即弥漫性轴索脑损伤(DABI),它描述了钝性损伤后大脑神经纤维撕裂的过程。大多数研究DABI的方案并未纳入针对该类病理情况的特定模型,这限制了它们识别DABI机制和合并症的能力。在本研究中,我们使用3-T临床扫描仪为大鼠模型中的DABI开发了一种磁共振成像(MRI)方案。我们将神经影像学结果与组织学和神经学评估进行了比较。在假手术组的10只大鼠和DABI组的10只大鼠样本中,我们在干预前和DABI诱导后48小时建立了神经严重程度评分。在DABI后的神经学评估之后,所有大鼠均接受MRI扫描,随后实施安乐死以进行组织学评估。正如预期的那样,神经学评估显示使用β-淀粉样前体蛋白(β-APP)标记物对DABI损伤具有高敏感性。然而,令人惊讶的是,我们发现与组织学方法相比,MRI方法在评估DABI损伤方面具有更高的敏感性。在DABI模型中具有病理变化的五个MRI参数中,我们发现与假手术大鼠相比,三个参数有显著变化,并且,如与其他模型的比较测试所示,MRI是最敏感的参数,甚至比组织学更敏感。我们预计,这种DABI方案将对未来的TBI和DABI研究产生重大影响,推动针对改善患者生活质量和长期预后的特定治疗研究。