Lopez-Rodriguez Ana Belen, Mela Virginia, Acaz-Fonseca Estefania, Garcia-Segura Luis Miguel, Viveros Maria-Paz
Departamento de Fisiología, Fisiología Animal (II), Facultad de Biología, Universidad Complutense, Madrid, Spain; Instituto Cajal (CSIC), Madrid, Spain.
Departamento de Fisiología, Fisiología Animal (II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
Exp Neurol. 2016 May;279:274-282. doi: 10.1016/j.expneurol.2016.03.018. Epub 2016 Mar 19.
The rates for traumatic brain injury (TBI) have risen in the last decade. Studies in animal models and clinical trials have not yet resulted in an effective treatment for TBI. Leptin, a 16kDa peptidic hormone is mainly known as a regulator of energy balance and has been shown to exert neuroprotective effects in different models of brain pathology. In this study, we have assessed whether leptin exerts protective actions in a TBI mouse model. In addition, the possible implication of CB2 cannabinoid receptor in leptin actions has been explored, since it is known that the endocannabinoid system interacts with leptin and actively participates in brain recovery after lesions.
Swiss (CD1) male mice were subjected to weigh-drop model for TBI. Prior to the lesion, mice were injected with an antagonist of CB2 receptor (AM630) or the vehicle and immediately after TBI, they received leptin or vehicle treatment. Data were analyzed using a two-way ANOVA or the non-parametric test Kruskal-Wallis when appropriate. For correlation analyses, Spearman's rho test, followed by linear regression test, was used.
TBI induced a neurological deficit, which was improved by leptin treatment. Leptin recovered several parameters affected by TBI, including the expression of cannabinoid receptors, axonal injury marker and neuroinflammatory components. The effects of leptin were prevented or reduced when it was administered in combination with the CB2 receptor antagonist, AM630.
Since some of the beneficial effects of leptin were not evident in the presence of AM630, our results suggest that CB2 receptor might be involved in the full expression of the neuroprotective effects of the hormone. These findings open new avenues for the study of leptin as a therapeutic treatment for TBI and enhance the importance of CB2 receptor in TBI pathophysiology and recovery.
在过去十年中，创伤性脑损伤（TBI）的发生率有所上升。动物模型研究和临床试验尚未产生针对TBI的有效治疗方法。瘦素是一种16kDa的肽类激素，主要作为能量平衡的调节剂，并且已被证明在不同的脑病理模型中发挥神经保护作用。在本研究中，我们评估了瘦素在TBI小鼠模型中是否发挥保护作用。此外，还探讨了CB2大麻素受体在瘦素作用中的可能影响，因为已知内源性大麻素系统与瘦素相互作用并积极参与损伤后的脑恢复。
瑞士（CD1）雄性小鼠接受TBI的重量落体模型。在损伤前，给小鼠注射CB2受体拮抗剂（AM630）或赋形剂，TBI后立即给予瘦素或赋形剂治疗。在适当的时候，使用双向方差分析或非参数检验Kruskal-Wallis分析数据。对于相关性分析，使用Spearman秩相关检验，随后进行线性回归检验。
TBI诱导神经功能缺损，瘦素治疗可改善该缺损。瘦素恢复了受TBI影响的几个参数，包括大麻素受体的表达、轴突损伤标志物和神经炎症成分。当瘦素与CB2受体拮抗剂AM630联合使用时，其作用被预防或减弱。
由于在存在AM630的情况下瘦素的一些有益作用不明显，我们的结果表明CB2受体可能参与了该激素神经保护作用的完全表达。这些发现为研究瘦素作为TBI的治疗方法开辟了新途径，并增强了CB2受体在TBI病理生理学和恢复中的重要性。
