One of quite a few by now. If not for politics a lot of people would be
saved from unnecessary cell loss. .....
Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn
rat model of acute severe asphyxia
José Martínez-Orgado, , a, Beatriz Fernández-Frutosc, Rita Gonzáleza, Eva
Romeroc, Leire Urigüenc, Julián Romerob and M. Paz Viverosc
a Area de Pediatría y Neonatología, Fundación Hospital Alcorcón, Avda.
Budapest 1, 28990 Alcorcón, Madrid, Spain
b Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón,
c Departamento de Biología Animal II (Fisiología Animal), Facultad de
Ciencias Biológicas, Universidad Complutense, Madrid, Spain
Accepted 11 April 2003. ; Available online 20 June 2003.
This study was designed to evaluate the neuroprotective effect of the
cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in
newborn rats. The left common carotid artery was ligated in anaesthetised
7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen
for 10 min. Pups recovering from asphyxia were s.c. administered vehicle
(n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor
antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served
as controls (n=12). Coronal sections of the brain were obtained on the 14th
day after surgery and observed under light microscope after Nissl or
Fluoro-Jade B (FJB) staining, to respectively quantify surviving or
degenerating neurones in the CA1 area of the hippocampus and parietal
cortex. Acute asphyxia led to early neurone loss amounting to 19% in the
hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed
neurone loss occurred in the proportions 13% in the hippocampus and 20% in
the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully
prevented by WIN-55212 administration. Co-administration of SR141716 failed
to modify the protective effect of WIN-55212 on early neuronal death, but
abolished the WIN-55212-induced prevention of delayed neuronal death. We
conclude that when administered after acute severe asphyxia in newborn rats,
WIN-55212 shows a neuroprotective effect, reducing both early and delayed
neurone loss. This effect is achieved through two parallel CB1-dependent
and -independent mechanisms.
Author Keywords: Cannabinoids; CB receptors; Hypoxia-ischemia; Brain damage;
Neuroscience classification codes: Disorders of the nervous system, Ischemia
Corresponding author. Tel.: +34-91-621-9968.
johnYYYcoe at tpg.com.au
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