The cannabinoid receptor agonist WIN 55,212-2 reduces the initial cerebral damage after hypoxic-ischemic injury in fetal lambs

被引:26
作者
Alonso-Alconada, Daniel [1 ]
Alvarez, Francisco J. [2 ]
Alvarez, Antonia [1 ]
Mielgo, Victoria E. [2 ]
Goni-de-Cerio, Felipe [1 ]
Rey-Santano, Maria C. [2 ]
Caballero, Amale [3 ]
Martinez-Orgado, Jose [4 ]
Hilario, Enrique [1 ]
机构
[1] Univ Basque Country, Dept Cell Biol & Histol, Sch Med, Leioa, Vizcaya, Spain
[2] Hosp Cruces, Unit Perinatal Res, Baracaldo, Vizcaya, Spain
[3] Univ Basque Country, Dept Neurosci, Sch Med, Leioa, Vizcaya, Spain
[4] Hosp Puerta Hierro, Madrid, Spain
关键词
Hypoxia-ischemia; Brain damage; Apoptosis; Cannabinoid; FIBRILLARY ACIDIC PROTEIN; DELAYED NEURONAL DEATH; PROGRAMMED CELL-DEATH; CB2; RECEPTOR; BRAIN-DAMAGE; THERAPEUTIC STRATEGIES; MORPHOLOGICAL-CHANGES; MATTER ASTROCYTES; RAT MODEL; PRETERM;
D O I
10.1016/j.brainres.2010.09.050
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The aim of the present work was to evaluate in an early time point the effect of the cannabinoid agonist WIN 55,212-2 after hypoxic ischemic (HI) brain injury induced by partial occlusion of the umbilical cord of premature fetal lambs. Lambs were assigned to three experimental groups: one SHAM group: non-injured animals, and two hypoxic ischemic groups that received a dose of 0.01 mu g/kg WIN 55,212-2 (HI + WIN group) or not (HI + VEH) after 60 min of a hypoxic ischemic event. All animals were managed on mechanical ventilation for 3 h and then sacrificed. Brains were perfusion-fixed and different regions separated for regional cerebral blood flow measurement, apoptosis quantification by TUNEL method and S-100 protein analysis by flow cytometry. The number of apoptotic cells was lower in the HI + WIN group in all regions studied. Moreover, animals treated with the cannabinoid agonist showed higher values in the percentage of S-100 positive cells in all regions, except,in the cortex. In both studies we obtained similar values between SHAM group and HI + WIN group. Our results suggest that the administration of the cannabinoid agonist WIN 55,212-2 after hypoxic ischemic brain injury in preterm lambs decreases brain injury reducing the delayed cell death and glial damage. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:150 / 159
页数:10
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