Abstract
Background and aims: Granulocyte-colony stimulating factor (G-CSF) has been shown to exert neuroprotective effects in several in vivo models of brain injury mediated by its anti-apoptotic, anti-inflammatory, neurotrophic and excitoprotective action. However, the effect of G-CSF on functional abilities following neonatal hypoxia-ischemia (HI) is still uncertain. The aim of this study was to evaluate the effect of G-CSF on HI-induced long-term behavioral impairment (motor and memory ability) and brain injury.
Methods: Seven-day-old rats underwent unilateral, permanent carotid artery ligation followed by 1h of hypoxia and were divided into 3 groups: A (n=7, sham-operated), B (n=14, HI), and C (n=14, HI-GCSF), post-treated with G-CSF (50 μg/kg). Behavioral tests were performed from days P50-P65, during which motor activity (rota-rod) and learning/memory function (water maze) were examined. Histological analysis was performed at the level of dorsal hippocampus according to a semiquantitative 5-point scale.
Results: HI resulted in significant motor function (102.5±14.8sec) and spatial reference (37.4±5.5sec) and working memory impairment (30.8±4sec) compared to sham-operated rats (rota-rod:213±22sec, reference:14.7±1.8 and working memory:14.2±2sec) (p< 0.05). G-CSF-treated rats exhibited significantly improved performance in rota-rod (167.7±14.8sec) and water maze (reference: 11.7±1.3 and working memory:17.3±5.5sec) tests, almost reaching the performance of sham-operated animals. Neonatal HI resulted in extensive neuronal damage that was limited after G-CSF administration (p< 0.05).
Conclusions: G-CSF administration exerts long-term neuroprotective effect by reducing the HI-induced neuronal injury and neurological deficits. Longer-latency effects implicated in neuroprotective role of G-CSF, such as neurogenesis or neurotrophic action, should be investigated.
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Griva, M., Kokaraki, G., Georgiou, T. et al. 112 G-Csf Prevents Long-Term Behavioral Deficits and Brain Injury Following Neonatal Hypoxia-Ischemia in Rats. Pediatr Res 68 (Suppl 1), 60 (2010). https://doi.org/10.1203/00006450-201011001-00112
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DOI: https://doi.org/10.1203/00006450-201011001-00112