中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (9): 1961-1967.doi: 10.4103/1673-5374.367846

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

美洛昔康对大鼠短暂性脑缺血的神经保护:抗炎治疗的两面性

  

  • 出版日期:2023-09-15 发布日期:2023-03-06
  • 基金资助:
    MINECO和FEDER基金;Neural Therapies SL

Neuroprotective effects of meloxicam on transient brain ischemia in rats: the two faces of anti-inflammatory treatments

Irene Fernández Ugidos1, †, Paloma González-Rodríguez1, María Santos-Galdiano1, 2, Enrique Font-Belmonte1, ‡, #br# Berta Anuncibay-Soto1, §, Diego Pérez-Rodríguez1, ||, José Manuel Gonzalo-Orden1, 3, Arsenio Fernández-López1, †#br#   

  1. 1Área de Biología Celular, Instituto de Biomedicina, Campus de Vegazana s/n, Universidad de León, León, Spain; 2Neural Therapies SL. Edif. Institutos de Investigación. Planta baja. Local B43. Campus de Vegazana s/n. León. Spain; 3Department of Medicina, Cirugía y Anatomía Veterinaria, University of León, León, Spain
  • Online:2023-09-15 Published:2023-03-06
  • Contact: Arsenio Fernández-López, PhD, aferl@unileon.es.
  • Supported by:
    This work was supported by MINECO and FEDER funds: ref CPP2021-008855 and RTC-2015-4094-1, Junta de Castilla y León ref.  LE025P17, and Neural Therapies SL, ref. NT-Dev-01 (all to AFL and JMGO).

摘要:

炎症反应在缺血性损伤后的神经保护和再生中起着重要作用;然而,非甾体抗炎药在缺血性脑损伤中的使用是有益还是有害尚存在争议。基于抗炎药美洛昔康有抑制两种环氧化酶异构体(1和2)的能力,其可能是调节缺血后炎症的有希望策略。实验观察了美洛昔康在大鼠短暂性局灶性脑缺血再灌注48h和7d后的神经保护作用,以及治疗对胶质瘢痕和神经再生的影响,如脑室下区新祖细胞的产生和受损区域边缘的轴突萌发。结果显示,美洛昔康的神经保护作用在再灌注7天后仍然存在,即使其给药仅限于缺血后的头2天。此外,美洛昔康治疗调节了胶质瘢痕反应性,这与轴突萌发的增加相匹配。然而,这种治疗减少了神经元祖细胞的形成。此项研究讨论了缺血性脑损伤后抗炎治疗的双重作用,并为缺血性脑损伤后抗炎治疗的使用提供了一个新视角分析结果。

https://orcid.org/0000-0001-5557-2741 (Arsenio Fernández-López)

Abstract: The inflammatory response plays an important role in neuroprotection and regeneration after ischemic insult. The use of non-steroidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects. In this context, the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stroke, but its ability to inhibit both cyclooxygenase isoforms (1 and 2) could be a promising strategy to modulate post-ischemic inflammation. This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats, measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area. We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia. Moreover, meloxicam treatment modulated glial scar reactivity, which matched with an increase in axonal sprouting. However, this treatment decreased the formation of neuronal progenitor cells. This study discusses the dual role of anti-inflammatory treatments after stroke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

Key words: anti-inflammatories, astrocyte, axonal sprouting, cylinder test, doublecortin, focal brain ischemia, glial scar, inflammation, neuroprotection, new neuron generation, transient stroke