Imaging of White Matter Injury Correlates with Plasma and Tissue Biomarkers in Pediatric Porcine Model of Traumatic Brain Injury.
Imaging of White Matter Injury Correlates with Plasma and Tissue Biomarkers in Pediatric Porcine Model of Traumatic Brain Injury.
复制标题
在小儿猪创伤性脑损伤模型中，白质损伤的成像与血浆和组织生物标志物相关。
DOI：
10.1089/neu.2022.0178
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发表时间：
2023
影响因子：
4.2
通讯作者：
Kilbaugh,ToddJ
中科院分区：
文献类型：
--
作者：
Shin,SamuelS;Chawla,Sanjeev;Jang,DavidH;Mazandi,VanessaM;Weeks,MKatie;Kilbaugh,ToddJ
创伤性脑损伤（TBI）会导致严重的白质损伤，各种啮齿动物和人类临床研究都已对其进行了表征。然而，TBI 后儿童大脑成像变化的确切时间过程及其与损伤和细胞功能生物标志物的关系尚不清楚。为了使用在大小和解剖特征方面与人类儿童大脑相当的有效 TBI 模型来研究主要白质结构的变化，我们使用了 4 周大的儿童猪损伤模型，具有受控皮质冲击 (CCI)。使用扩散张量成像差分纤维束成像，我们显示了受伤后第 1 天到第 30 天之间主要白质纤维束（例如放射冠和额枕下束）的进行性各向异性变化。此外，相关纤维束成像显示大部分双侧辐射冠与细胞呼吸标志物呈正相关。相反，双侧放射冠与损伤的血浆生物标志物如神经丝光或胶质纤维酸性蛋白呈负相关。鉴于白质较高的完整性预计与较低的损伤生物标志物相关，这些是预期的相关发现。然后，我们研究了磁共振波谱结果，并报告 30 天时，挫伤周围皮质、皮质下白质、放射冠、丘脑、膝部和胼胝体压部的 N-乙酰天冬氨酸/肌酐 (NAA/Cr) 比率下降，表明存在损伤。这些区域的胆碱/肌酐比率也有所增加，表明膜周转速度很快。鉴于需要与人类儿科 TBI 相当的儿科 TBI 模型，这些数据支持在未来的治疗剂研究中使用具有 CCI 的儿科猪模型。该模型将使未来的 TBI 研究人员能够快速将我们的临床前研究结果转化为儿科 TBI 的临床试验。
Traumatic brain injury (TBI) causes significant white matter injury, which has been characterized by various rodent and human clinical studies. The exact time course of imaging changes in a pediatric brain after TBI and its relation to biomarkers of injury and cellular function, however, is unknown. To study the changes in major white matter structures using a valid model of TBI that is comparable to a human pediatric brain in terms of size and anatomical features, we utilized a four-week-old pediatric porcine model of injury with controlled cortical impact (CCI). Using diffusion tensor imaging differential tractography, we show progressive anisotropy changes at major white matter tracts such as the corona radiata and inferior fronto-occipital fasciculus between day 1 and day 30 after injury. Moreover, correlational tractography shows a large part of bilateral corona radiata having positive correlation with the markers of cellular respiration. In contrast, bilateral corona radiata has a negative correlation with the plasma biomarkers of injury such as neurofilament light or glial fibrillary acidic protein. These are expected correlational findings given that higher integrity of white matter would be expected to correlate with lower injury biomarkers. We then studied the magnetic resonance spectroscopy findings and report decrease in a N-acetylaspartate/creatinine (NAA/Cr) ratio at the pericontusional cortex, subcortical white matter, corona radiata, thalamus, genu, and splenium of corpus callosum at 30 days indicating injury. There was also an increase in choline/creatinine ratio in these regions indicating rapid membrane turnover. Given the need for a pediatric TBI model that is comparable to human pediatric TBI, these data support the use of a pediatric pig model with CCI in future investigations of therapeutic agents. This model will allow future TBI researchers to rapidly translate our pre-clinical study findings into clinical trials for pediatric TBI.