Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury.
Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury.
复制标题
丁丙诺啡在弥漫性创伤性脑损伤后急性改变小胶质细胞和星形胶质细胞。
DOI：
10.1038/s41598-021-88030-z
复制
发表时间：
2021-04-21
影响因子：
4.6
通讯作者：
Lafrenaye A
中科院分区：
文献类型：
--
作者：
Ryu J;Stone P;Lee S;Payne B;Gorse K;Lafrenaye A
创伤性脑损伤（TBI）是一种常见的现象，占显着的成本和不良的健康影响。虽然有关于创伤性脑损伤后病灶病理学的信息，但缺乏更多扩散过程的知识，特别是关于镇痛剂如何影响这种病理学的知识。由于丁丙诺啡是实验性TBI模型中最常用的镇痛剂，因此本研究研究了阿片类镇痛剂丁丙诺啡（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。我们利用了一个模型的中央流体冲击损伤（CFPI）的成年雄性大鼠用单次皮下推注的Bup-SR-Lab或生理盐水损伤后15分钟。在损伤后1天进行显微镜评估。在处死之前，脑室内输注细胞不可渗透的葡聚糖，以评估神经元膜破坏。轴突损伤通过研究顺行运输淀粉样前体蛋白的标记来评估。通过分析Iba-1 +小胶质细胞和GFAP +星形胶质细胞的组织学/形态学特征以及两个感兴趣区域（ROIs）中的细胞因子水平来评估神经炎症。通过评价髓鞘碱性蛋白（MBP）的表达和MBP +髓鞘碎片的倾向来评估髓鞘病理学。急性生理学数据显示，除了与生理盐水相比，Bup治疗动物在cFPI后体重减轻减少外，组间无差异。治疗组之间的轴突损伤或膜破裂无明显差异。细胞因子水平在Bup和盐水处理的动物之间是一致的，然而，小胶质细胞和星形胶质细胞在Bup处理后1d显示区域特异性组织学变化。髓鞘的完整性和整体MBP的表达没有表现出任何差异Bup和盐水处理的动物，但有显着的区域差异MBP的表达之间的皮层和丘脑。这些数据表明Bup治疗对CFPI后体重的影响以及Bup相关小胶质细胞和星形胶质细胞改变的潜在区域特异性，但在损伤后1天其他急性病理学变化非常小。总体而言，这项初步研究表明，在临床前工作中使用Bup-SR-Lab确实对急性神经胶质病理学有影响，但是，需要进行更长期的研究来评估Bup治疗对更慢性病理学进展的潜在影响。
Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As buprenorphine is the most commonly used analgesic in experimental TBI models, this study investigated the acute effects of the opioid analgesic buprenorphine (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. We utilized a model of central fluid percussion injury (CFPI) in adult male rats treated with a single subcutaneous bolus of Bup-SR-Lab or saline 15 min post-injury. Microscopic assessments were performed at 1 day post-injury. Cell impermeable dextran was infused intraventricularly prior to sacrifice to assess neuronal membrane disruption. Axonal injury was assessed by investigating labeling of the anterogradely transported amyloid precursor protein. Neuroinflammation was assessed by analyzing Iba-1 + microglial and GFAP + astrocyte histological/morphological features as well as cytokine levels in both regions of interest (ROIs). Myelin pathology was assessed by evaluating the expression of myelin basic protein (MBP) and the propensity of MBP + myelin debris. Acute physiologic data showed no difference between groups except for reduction in weight loss following cFPI in Bup treated animals compared to saline. There were no discernable differences in axonal injury or membrane disruption between treatment groups. Cytokine levels were consistent between Bup and saline treated animals, however, microglia and astrocytes revealed region specific histological changes at 1d following Bup treatment. Myelin integrity and overall MBP expression showed no differences between Bup and saline treated animals, but there were significant regional differences in MBP expression between the cortex and thalamus. These data suggest effects of Bup treatment on weight following CFPI and potential regional specificity of Bup-associated microglial and astrocyte alterations, but very little change in other acute pathology at 1-day post-injury. Overall, this preliminary study indicates that use of Bup-SR-Lab in preclinical work does have effects on acute glial pathology, however, longer term studies will be needed to assess potential effects of Bup treatment on more chronic pathological progressions.
登录
查看更多内容
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。
影响因子：
9.3
作者：
Byrnes KR;Loane DJ;Stoica BA;Zhang J;Faden AI
通讯作者：
Faden AI
影响因子：
9.8
作者：
Dahan, A;Yassen, A;Danhof, M
通讯作者：
Danhof, M
影响因子：
7.6
作者：
Falcon, Edgardo;Browne, Caroline A.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
6
作者：
Corkrum, Michelle;Rothwell, Patrick E.;Araque, Alfonso
通讯作者：
Araque, Alfonso
影响因子：
1
作者：
Dooley, S. Bryce;Aarnes, Turi K.;Hubbell, John A. E.
通讯作者：
Hubbell, John A. E.