Neuronano Research Center, Department of Experimental Medical Research, Faculty of Medicine, Lund University, Medicon Village, Building 404 A2, Scheelevägen 2, S-223 81 Lund, Sweden.
Neuronano Research Center, Department of Experimental Medical Research, Faculty of Medicine, Lund University, Medicon Village, Building 404 A2, Scheelevägen 2, S-223 81 Lund, Sweden.
Acta Biomater. 2018 Jan;65:137-149. doi: 10.1016/j.actbio.2017.10.020. Epub 2017 Oct 14.
Gelatin coating of brain implants is known to provide considerable benefits in terms of reduced inflammatory sequalae and long-term neuroprotective effects. However, the mechanisms for gelatin's protective role in brain injury are still unknown. To address this question, cellular and molecular markers were studied with quantitative immunohistochemical microscopy at acute (<2hours, 1, 3days), intermediate (1-2 weeks) and long-term time points (6 weeks) after transient insertion of stainless steel needles into female rat cortex cerebri with or without gelatin coating. Compared to non-coated controls, injuries caused by gelatin coated needles showed a significantly faster resolution of post-stab bleeding/leakage and differential effects on different groups of microglia cells. While similar levels of matrix metalloproteinase (MMP-2 and MMP-9, two gelatinases) was found for coated and noncoated needle stabs during the first week, markedly increased levels of both MMPs was seen for gelatin-coated but not non-coated needle stabs after 2weeks. Neuronal populations and activated astrocytes were largely unaffected. In conclusion, the beneficial effects of gelatin may be the combined results of faster healing of the blood brain barrier curtailing leakage of blood borne molecules/cells into brain parenchyma and to a modulation of the microglial population response favoring restitution of the injured tissue. These findings present an important therapeutic potential for gelatin coatings in various disease, injury and surgical conditions.
The neural interfaces field holds great promise to enable elucidation of neural information processing and to develop new implantable devices for stimulation based therapy. Currently, this field is struggling to find solutions for reducing tissue reactions to implanted micro and nanotechnology. Prior studies have recently shown that gelatin coatings lower activation of digestive microglia and mitigate the ubiquitous loss of neurons adjacent to implanted probes, both of which impede implant function. The underlying mechanisms remain to be elucidated, however. Our findings demonstrate for the first time that gelatin has a significant effect on the BBB by promoting rapid restoration of integrity after injury. Moreover, gelatin alters microglia phenotypes and modulates gelatinase activity for up to 2weeks favoring anti-inflammation and restoration of the tissue. Given the key importance of the BBB for normal brain functions, we believe our findings have substantial significance and will be highly interesting to researchers in the biomaterial field.
众所周知，在减少炎症后遗症和长期神经保护作用方面，脑植入物的明胶涂层具有很大的益处。然而，明胶在脑损伤中的保护作用的机制仍不清楚。为了解决这个问题，使用定量免疫组织化学显微镜研究了细胞和分子标记物，这些标记物在不锈钢针短暂插入雌性大鼠大脑皮质后，在急性（<2 小时、1 天、3 天）、中期（1-2 周）和长期（6 周）时间点进行了研究，有无明胶涂层。与未涂层对照相比，明胶涂层针引起的损伤显示出更快的止血/渗漏缓解，以及对不同类型小胶质细胞的不同影响。虽然在第一周内，涂层和未涂层针刺伤的基质金属蛋白酶（MMP-2 和 MMP-9，两种明胶酶）水平相似，但在 2 周后，仅在明胶涂层针刺伤时观察到两种 MMP 水平显著升高。神经元群体和激活的星形胶质细胞基本不受影响。总之，明胶的有益效果可能是血脑屏障更快愈合的综合结果，阻止血液来源的分子/细胞漏入脑实质，并调节小胶质细胞群体反应，有利于受损组织的恢复。这些发现为明胶涂层在各种疾病、损伤和手术条件下提供了重要的治疗潜力。
神经接口领域具有很大的潜力，可以阐明神经信息处理，并开发用于基于刺激的治疗的新植入式设备。目前，该领域正在努力寻找减少对植入的微纳技术的组织反应的解决方案。最近的研究表明，明胶涂层可以降低消化性小胶质细胞的激活，并减轻植入探针周围普遍存在的神经元丧失，这两者都会阻碍植入物的功能。然而，其潜在机制仍有待阐明。我们的研究结果首次表明，明胶通过促进受伤后迅速恢复完整性对血脑屏障有显著影响。此外，明胶改变小胶质细胞表型，并在长达 2 周的时间内调节明胶酶活性，有利于抗炎和组织恢复。鉴于 BBB 对正常大脑功能的重要性，我们相信我们的发现具有重要意义，并且对生物材料领域的研究人员将非常感兴趣。
