Sharma Pushpa, Su Yan A, Barry Erin S, Grunberg Neil E, Lei Zhang
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Rockville, Maryland, USA.
Int J Crit Illn Inj Sci. 2012 Sep;2(3):172-9. doi: 10.4103/2229-5151.100931.
Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria.
The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain.
Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days.
Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naïe rats were also examined by oligo-DNA microarrays.
NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naïe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases.
Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.
轻度创伤性脑损伤（mTBI）是平民和军人中的一个主要健康问题，原因如下：（1）缺乏有效的治疗方法；（2）我们对继发细胞损伤级联反应的进展了解不完整，这种级联反应会因细胞能量代谢不足和线粒体受损导致神经元细胞死亡。
本研究的目的是识别和描述导致受伤大脑中脑能量代谢改变的线粒体靶向基因。
将大鼠分为未受伤对照组或接受侧方流体冲击性脑损伤（2 - 2.5个大气压），并随访7天。
将大鼠分为未受伤对照组或接受侧方流体冲击性脑损伤（2 - 2.5个大气压），并随访7天。在创伤性脑损伤后3天和5天通过修订的神经严重程度量表（NSS - R）评估脑损伤的严重程度，并在创伤性脑损伤后7天进行免疫组织化学分析。还通过寡核苷酸DNA微阵列检查了创伤性脑损伤大鼠和未受伤大鼠海马体中线粒体靶向基因的表达谱。
与未受伤大鼠（3.9 ± 0.5）相比，创伤性脑损伤大鼠的NSS - R评分（5.4 ± 0.5）以及脑切片的苏木精和伊红染色表明存在轻度脑损伤。生物信息学和系统生物学分析显示31个失调基因，10条受影响的典型分子途径，包括一些参与氧化磷酸化线粒体酶、丝裂原活化蛋白激酶（MAP）、过氧化物酶体增殖物激活蛋白（PPAP）、凋亡信号传导的基因，以及与阿尔茨海默病和帕金森病长期增强相关的基因。
我们的结果表明，受伤大脑中失调的线粒体相关基因可能对未来旨在治疗创伤性脑损伤的治疗策略的开发具有临床应用价值。
Zotero 插件
