Department of Neuroscience, Karolinska Institutet, Retzius väg 8, S-171 77 Stockholm, Sweden(1); Department of Neuroscience and Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
Department of Molecular Neuroscience, George Mason University, Fairfax, VA, USA; Department of Psychology, George Mason University, Fairfax, VA, USA.
Brain Res. 2014 Jan 13;1542:195-205. doi: 10.1016/j.brainres.2013.10.047. Epub 2013 Nov 2.
The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. In this study we examined the expression of these genes in a rat model of penetrating TBI. The injury is produced by a controlled penetration of a 2mm thick needle-shaped object, which is accelerated with a pellet from an air gun. We used in situ hybridization and investigated the mRNA expression of BDNF and its receptors: the full-length and the truncated TrkB and p75(NTR), from 1 day to 8 weeks following penetrating TBI. In addition, the protein level of BDNF in frontal cortex and hippocampus was measured by reverse phase protein microarray (RPPM). The mRNA expression of BDNF and its receptors decreased in the hippocampus in the border zone ipsilateral to the injury while there was an increase in mRNA expression at the contralateral side. The increase in BDNF mRNA expression in the hippocampus was sustained for 2 weeks following injury, with the highest expression noted in the CA3 cell layer. Furthermore, the protein analysis by RPPM showed increased levels of BDNF in the frontal cortex and the hippocampus up to 2 weeks after TBI. At 8 weeks following injury there was an intense labeling of the truncated TrkB receptor and the p75(NTR) in the area surrounding the cavity. Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.
BDNF 参与创伤性脑损伤（TBI）后的神经保护、神经元修复和恢复的证据是充分的。我们之前已经表明，人类 BDNF 基因的多态性可预测穿透性 TBI 后的认知恢复和结果。穿透性 TBI 后 BDNF 及其受体的表达分布尚未得到研究。在这项研究中，我们在穿透性 TBI 的大鼠模型中检查了这些基因的表达。损伤是通过用空气枪的弹丸加速的 2 毫米厚的针状物体的受控穿透产生的。我们使用原位杂交技术，从穿透性 TBI 后 1 天到 8 周，研究了 BDNF 及其受体的 mRNA 表达：全长和截断的 TrkB 和 p75（NTR）。此外，通过反相蛋白质微阵列（RPPM）测量额皮质和海马体中 BDNF 的蛋白质水平。BDNF 及其受体的 mRNA 表达在损伤同侧的海马体的边界区减少，而对侧的 mRNA 表达增加。损伤后 2 周内，海马体中 BDNF mRNA 表达持续增加，在 CA3 细胞层中表达最高。此外，RPPM 的蛋白质分析显示，TBI 后 2 周内额皮质和海马体中的 BDNF 水平升高。损伤后 8 周时，在腔周围区域存在强烈的截断型 TrkB 受体和 p75（NTR）标记。我们的研究是第一个关于穿透性 TBI 后 BDNF 及其受体表达的报告，并表明它们的表达在急性损伤期后很长时间都发生了改变。需要进一步研究以调查这些受体的晚期表达是否有益还是有害。在任何情况下，这都表明有可能在慢性期影响脑损伤后的恢复，并开发可能改善 TBI 患者结果的治疗方法。
