Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion.
Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion.
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DOI：
10.1093/braincomms/fcad032
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
吡格列酮通过线粒体蛋白mitoNEET相互作用，以改善创伤性脑损伤后的脑生物能量学。为了提供有关吡格列酮在创伤性脑损伤后治疗效果的更广泛证据，当前的研究重点是在轻度脑挫伤模型中进行即时和延迟治疗。为了评估吡格列酮对皮质和海马体线粒体生物能量学的治疗效果，我们使用一种技术来分离总线粒体、富含胶质细胞的线粒体和突触线粒体的亚群。吡格列酮治疗最初在轻度可控皮质撞击后的0.25、3、12或24小时进行给药。在损伤后48小时，解剖同侧皮质和海马体，并分离线粒体组分。在总线粒体组分和突触组分中观察到最大线粒体呼吸因损伤导致的缺陷，并且在轻度可控皮质撞击后0.25小时进行吡格列酮治疗能够将呼吸恢复到假手术水平。虽然海马体组分中没有因损伤导致的缺陷，但我们确实发现，与溶媒处理的轻度可控皮质撞击组相比，轻度可控皮质撞击后3小时进行吡格列酮治疗能够显著增加最大线粒体生物能量学。然而，在轻度脑挫伤后3小时或24小时开始的延迟吡格列酮治疗并不能改善剩余的皮质组织。我们证明，在轻度局灶性脑挫伤后，早期开始吡格列酮治疗可以恢复突触线粒体缺陷。需要进一步研究以确定在轻度挫伤性创伤性脑损伤后，除了明显的皮质组织保留之外，吡格列酮在功能上的改善情况。
哈伯德等人报告称，一种分离总线粒体、富含胶质细胞的线粒体和突触线粒体亚群的工作流程表明，在小鼠创伤性脑损伤后突触线粒体变化明显。早期给予吡格列酮可以改善轻度脑挫伤后的线粒体生物能量学，尽管这些改善并没有转化为明显的组织保留。
Pioglitazone interacts through the mitochondrial protein mitoNEET to improve brain bioenergetics following traumatic brain injury. To provide broader evidence regarding the therapeutic effects of pioglitazone after traumatic brain injury, the current study is focused on immediate and delayed therapy in a model of mild brain contusion. To assess pioglitazone therapy on mitochondrial bioenergetics in cortex and hippocampus, we use a technique to isolate subpopulations of total, glia-enriched and synaptic mitochondria. Pioglitazone treatment was initially administered at either 0.25, 3, 12 or 24 h following mild controlled cortical impact. At 48 h post-injury, ipsilateral cortex and hippocampus were dissected and mitochondrial fractions were isolated. Maximal mitochondrial respiration injury-induced deficits were observed in total and synaptic fractions, and 0.25 h pioglitazone treatment following mild controlled cortical impact was able to restore respiration to sham levels. While there are no injury-induced deficits in hippocampal fractions, we do find that 3 h pioglitazone treatment after mild controlled cortical impact can significantly increase maximal mitochondrial bioenergetics compared to vehicle-treated mild controlled cortical impact group. However, delayed pioglitazone treatment initiated at either 3 or 24 h after mild brain contusion does not improve spared cortical tissue. We demonstrate that synaptic mitochondrial deficits following mild focal brain contusion can be restored with early initiation of pioglitazone treatment. Further investigation is needed to determine functional improvements with pioglitazone beyond that of overt cortical tissue sparing following mild contusion traumatic brain injury. Hubbard et al. report that a workflow to isolate total, glia-enriched, and synaptic mitochondrial subpopulations demonstrates that synaptic mitochondrial changes are apparent following traumatic brain injury in mice. Early pioglitazone administration can improve mitochondrial bioenergetics following mild brain contusion, although these improvements do not translate to overt tissue sparing.
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影响因子：
4.6
作者：
Hubbard, W. Brad;Harwood, Christopher L.;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
影响因子：
4.2
作者：
Kulbe, Jacqueline R.;Hill, Rachel L.;Hall, Edward D.
通讯作者：
Hall, Edward D.
影响因子：
6.1
作者：
Vekaria, Hemendra J.;Hubbard, W. Brad;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
影响因子：
2.5
作者：
Lee A;Hirabayashi Y;Kwon SK;Lewis TL Jr;Polleux F
通讯作者：
Polleux F
影响因子：
6.3
作者：
Singh, Indrapal N.;Sullivan, Patrick G.;Hall, Edward D.
通讯作者：
Hall, Edward D.