Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden; International Experimental CNS Injury & Repair (IECNSIR), University Hospital, Uppsala University, Uppsala, Sweden.
Laboratory of Clinical and Experimental Neuroscience (LaNCE), University of the Basque Country UPV/EHU, Leioa, Vizcaya, Spain; Faculty of Health Science, Universidad Autónoma de Chile, Santiago de Chile, Chile.
Int Rev Neurobiol. 2017;137:47-63. doi: 10.1016/bs.irn.2017.08.005. Epub 2017 Nov 3.
Influence of iron oxide magnetic nanoparticles (IOMNPs, 10nm in diameter, 0.25 or 0.50mg/mL in 100μL, i.v.) on the blood-brain barrier (BBB) permeability, edema formation, and neuronal or glial changes within 4-24h after administration was examined in normal rats and after a focal spinal cord injury (SCI). Furthermore, effect of cerebrolysin, a balanced composition of several neurotrophic factors, and active peptide fragments was also evaluated on IOMNP-induced changes in central nervous system (CNS) pathology. The SCI was inflicted in rats by making a longitudinal incision into the right dorsal horn of the T10-11 segments and allowed to survive 4 or 24h after trauma. Cerebrolysin (2.5mL/kg, i.v.) was given either 30min before IOMNP injection in the 4-h SCI group or 4h after injury in the 24-h survival groups. Control group received cerebrolysin in identical situation following IOMNP administration. In all groups, leakage of serum albumin in the CNS as a marker of BBB breakdown and activation of astrocytes using glial fibrillary acidic protein was evaluated by immunohistochemistry. The neuronal injury was examined by Nissl staining. The IOMNPs alone in either low or high doses did not induce CNS pathology either following 4 or 24h after administration. However, administration of IOMNPs in SCI group slightly enhanced the pathological changes in the CNS after 24h but not 4h after trauma. Cerebrolysin treatment markedly attenuated IOMNP-induced aggravation of SCI-induced cord pathology and induced significant neuroprotection. These observations are the first to show that IOMNPs are safe for the CNS and cerebrolysin treatment prevented CNS pathology following a combination of trauma and IOMNP injection. This indicated that cerebrolysin might be used as adjunct therapy during IOMNP administration in disease conditions, not reported earlier.
在正常大鼠和脊髓损伤（SCI）后，研究了直径为 10nm、浓度为 0.25 或 0.50mg/mL（100μL 中）的氧化铁磁性纳米颗粒（IOMNPs）在给药后 4-24 小时内对血脑屏障（BBB）通透性、水肿形成以及神经元或神经胶质变化的影响。此外，还评估了神经生长因子的平衡组成物脑活素和活性肽片段对 IOMNP 引起的中枢神经系统（CNS）病理变化的影响。SCI 通过在 T10-11 节段的右侧背角做一个纵切口造成，在创伤后 4 或 24 小时后使其存活。脑活素（2.5mL/kg，iv）在 4 小时 SCI 组的 IOMNP 注射前 30 分钟或 24 小时存活组的损伤后 4 小时给予。对照组在给予 IOMNP 后给予脑活素，情况相同。在所有组中，通过免疫组织化学评估血清白蛋白作为 BBB 破裂的标志物漏出和使用胶质纤维酸性蛋白的星形胶质细胞激活。通过尼氏染色检查神经元损伤。单独使用 IOMNP 低或高剂量在给药后 4 或 24 小时后均不会引起 CNS 病理学改变。然而，在 SCI 组中给予 IOMNP 会在创伤后 24 小时而不是 4 小时轻微增强 CNS 的病理变化。脑活素治疗明显减轻了 IOMNP 诱导的 SCI 诱导的脊髓病理学恶化，并诱导了明显的神经保护作用。这些观察结果是首次表明 IOMNPs 对 CNS 是安全的，并且脑活素治疗可防止创伤和 IOMNP 注射联合后的 CNS 病理学改变。这表明，在疾病状态下，脑活素可能在 IOMNP 给药期间作为辅助治疗使用，这在以前的报道中尚未提及。
