Glial Cell-Mediated Deterioration and Repair of the Nervous System after Traumatic Brain Injury in a Rat Model as Assessed by Positron Emission Tomography
Glial Cell-Mediated Deterioration and Repair of the Nervous System after Traumatic Brain Injury in a Rat Model as Assessed by Positron Emission Tomography
复制标题
DOI：
10.1089/neu.2009.1196
复制
发表时间：
2010-08-01
影响因子：
4.2
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Yu, Iwae;Inaji, Motoki;Suhara, Tetsuya
外伤性脑损伤（TBI）是中枢神经系统最严重的退行性病理之一，目前尚未建立能够在机制基础上评估TBI的体内指标。本研究的目的是通过纵向正电子发射断层扫描（PET）研究大鼠创伤性脑损伤模型中神经炎症变化及其与创伤性损伤神经元功能破坏的联系。根据外侧液体冲击脑损伤方案，在开颅大鼠单侧额叶皮层诱导TBI。使用[F-18]氟乙基- daa1106作为转运蛋白（TSPO）的PET示踪剂，可以证明损伤的炎症反应，在撞击后1周达到峰值。这种改变与PET用[F-18]氟脱氧葡萄糖评估的代谢缺陷相似，但冲击与非冲击额叶皮质之间的TSPO水平差异是外侧代谢差异的三倍以上，表明TSPO成像在敏感检测创伤后病理方面的优势。对比PET，放射自显影。免疫组织化学研究表明，增生性小胶质细胞和巨噬细胞对撞击附近急性TSPO信号的主要贡献。星形胶质细胞也在坏死炎症周围形成TSPO阳性胶质瘢痕，并在晚期双侧外囊和内囊聚集pet可检测到的TSPO信号，推测与弥漫性轴索损伤有关。这些观察结果支持TSPO-PET作为一种基于成像的临床前和临床生物标志物检测在TBI中的适用性，并表明其在与新兴的抗炎和免疫调节治疗相结合时阐明胶质细胞对损伤反应的侵袭性和保护性作用的潜在能力。
Traumatic brain injury (TBI) is one of the most acute degenerative pathologies in the central nervous system, and in vivo indices enabling an assessment of TBI on a mechanistic basis have yet to be established. The aim of this work was to pursue neuroinflammatory changes and their link to functional disruptions of traumatically-damaged neurons in a rat model of TBI by longitudinal positron emission tomographic (PET) assays. TBI was induced in the unilateral frontal cortex of craniotomied rats according to a lateral fluid percussion brain injury protocol. The use of [F-18] fluoroethyl-DAA1106 as a PET tracer for translocator protein (TSPO) permitted demonstration of the inflammatory response to the injury, peaking at 1 week after impact. This alteration was parallel to metabolic deficits assessed by PET with [F-18] fluorodeoxyglucose, but the difference in TSPO levels between impacted and non-impacted frontal cortices was more than threefold of the interlateral metabolic difference, indicating superiority of TSPO imaging for sensitive detection of post-traumatic pathologies. Comparative PET, autoradiographic. and immunohistochemical investigations illustrated the primary contribution of hypertrophic microglia and macrophages to acute TSPO signals in the vicinity of the impact. Astrocytes also formed a TSPO-positive glial scar encompassing necrotic inflammation, and were clustered with PET-detectable TSPO signals in the bilateral external and internal capsules at late stages, putatively reacting with diffuse axonal injury. These observations support the applicability of TSPO-PET as an imaging-based preclinical and clinical biomarker assay in TBI, and indicate its potential capability to clarify aggressive and protective roles of glial responses to injury when combined with emerging anti-inflammatory and immunomodulatory treatments.