Post-Injury Buprenorphine Administration Is Associated with Long-Term Region-Specific Glial Alterations in Rats.

Post-Injury Buprenorphine Administration Is Associated with Long-Term Region-Specific Glial Alterations in Rats.
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DOI:
10.3390/pharmaceutics14102068
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发表时间:
2022-09-28
期刊:
影响因子:
5.4
通讯作者:
Lafrenaye A
Lafrenaye A
中科院分区:
医学2区
文献类型:
--
作者:
Ryu J;Jeizan P;Ahmed S;Ehsan S;Jose J;Regan S;Gorse K;Kelliher C;Lafrenaye A

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脑外伤(TBI)是死亡和残疾的主要原因。虽然以前的研究已经完成了关于局灶性病理TBI后,有一个关于镇痛药的作用和它们对损伤病理学的影响的信息缺乏。丁丙诺啡(Bup)是一种阿片类镇痛药,是实验性TBI模型中常用的镇痛药。我们先前的研究调查了丁丙诺啡缓释Lab(Bup-SR-Lab)对弥漫性神经元/神经胶质病理学、神经炎症、细胞损伤和全身生理学的急性作用。本研究利用成年雄性大鼠中枢液压冲击损伤(cFPI)模型,研究了TBI后4周Bup-SR-Lab治疗的长期慢性结局。如我们在急性研究中所做的那样,对生理变化、神经元损伤、皮质和丘脑细胞因子表达、小胶质细胞和星形胶质细胞形态学变化以及髓鞘改变进行了组织学评估。在本研究中,还在损伤前和损伤后4周进行了胡须营养任务(WNT),以评估生理盐水或Bup-SR-Lab治疗后体感敏感性的变化。无论部位或损伤如何,Bup-SR-Lab治疗对损伤后4周的整体生理学或神经元损伤没有影响,对体感敏感性也没有任何显著影响。然而,与盐水处理的动物相比,观察到Bup-SR-Lab处理的IL-4细胞因子表达更高。小胶质细胞和星形胶质细胞也表现出与Bup-SR-Lab治疗相关的区域特异性形态学改变,其中皮质小胶质细胞和丘脑星形胶质细胞特别容易受到Bup介导的变化的影响。在Bup-SR-Lab治疗后,关于髓鞘完整性和特定髓鞘碱性蛋白(MBP)亚型表达的变化,存在可辨别的损伤特异性和区域特异性差异。这项研究表明,使用Bup-SR-Lab可以影响TBI诱导的神经胶质细胞的变化,在弥漫性脑损伤后4周以区域特异性的方式。
Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manner 4w following diffuse brain injury.
延迟的MGLUR5激活限制了创伤性脑损伤后神经炎症和神经退行性的限制。
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