Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury.
Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury.
复制标题
DOI：
10.1007/s12035-018-1276-5
复制
发表时间：
2019-04
影响因子：
5.1
通讯作者：
Evanson NK
中科院分区：
文献类型：
--
作者：
McGuire JL;DePasquale EAK;Watanabe M;Anwar F;Ngwenya LB;Atluri G;Romick-Rosendale LE;McCullumsmith RE;Evanson NK
外伤性脑损伤（TBI）是世界范围内导致死亡和长期残疾的主要原因。虽然创伤性脑损伤后的慢性残疾很常见，但有效的治疗方法仍然难以捉摸，而且慢性创伤性脑损伤的病理生理机制也不太清楚。脑外伤后早期，由于不受调节的离子释放、线粒体损伤和分子运输中断，脑代谢被破坏。这种代谢紊乱至少是部分脑损伤病理的原因。然而，目前尚不清楚代谢损伤在损伤后期是如何持续或普遍存在的。采用非靶向1H-NMR代谢组学方法，研究了慢性脑损伤大鼠外侧液击模型的离体海马、纹状体、丘脑、额叶皮层和脑干组织。我们发现海马和丘脑代谢物组织浓度的改变与能量代谢和兴奋性神经传递的失调相一致。此外，差异相关分析提供了代谢失调的额外证据，尤其是在脑干和额叶皮层，表明损伤的代谢后果是持续和广泛的。有趣的是，网络变化的模式是区域性的。损伤后休息时不同脑结构的个体代谢特征可能反映了不同的代偿机制，以满足不同脑区域的代谢需求。
Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking. This metabolic disruption causes at least part of the TBI pathology. However, it is not clear how persistent or pervasive metabolic injury is at later stages of injury. Using untargeted 1H-NMR metabolomics, we examined ex vivo hippocampus, striatum, thalamus, frontal cortex, and brainstem tissue in a rat lateral fluid percussion model of chronic brain injury. We found altered tissue concentrations of metabolites in the hippocampus and thalamus consistent with dysregulation of energy metabolism and excitatory neurotransmission. Furthermore, differential correlation analysis provided additional evidence of metabolic dysregulation, most notably in brainstem and frontal cortex, suggesting that metabolic consequences of injury are persistent and widespread. Interestingly, the patterns of network changes were region-specific. The individual metabolic signatures after injury in different structures of the brain at rest may reflect different compensatory mechanisms engaged to meet variable metabolic demands across brain regions.
登录
查看更多内容
DOI：
10.3389/fnene.2013.00008
发表时间：
2013-10-04
期刊：
Frontiers in neuroenergetics
影响因子：
--
作者：
Bartnik-Olson BL;Harris NG;Shijo K;Sutton RL
通讯作者：
Sutton RL
影响因子：
3.4
作者：
del Olmo, N;Suárez, LM;Solís, JM
通讯作者：
Solís, JM
影响因子：
4.2
作者：
Casey, Paula A.;Mckenna, Mary C.;Robertson, Courtney L.
通讯作者：
Robertson, Courtney L.
影响因子：
3
作者：
Aiello, GL;Bach-y-Rita, P
通讯作者：
Bach-y-Rita, P
影响因子：
5.2
作者：
Calvetti D;Somersalo E
通讯作者：
Somersalo E