206 Combination Therapy with Erythropoietin and N-Acetylcysteine Provides Pronounced Improvement of Long Lasting Sensorimotor and Neuropathological Disturbances following Perinatal Asphyxia in Rats

Abstract

Background: Perinatal asphyxia (PA) accounts for the majority of developmental and cognitive deficits. Various therapeutic interventions after hypoxia-ischemia (HI) have been shown to reduce brain injury in the short-term perspective, although long-term functional and structural improvements are still uncertain. Objective: The aim of this study was to evaluate the neuroprotective efficiency of erythropoietin (EPO), N-acetylcysteine (NAC) and their combination after neonatal HI with respect to long term (neuropathology and sensorimotor function) outcome. Methods: 7 days old rats were separated into 5 groups: A (control), neither ligated nor exposed to hypoxia, B (HI) ligated and exposed to hypoxia, C, D and E ligated, exposed to hypoxia and treated respectively with NAC (100mg/kg), EPO (2000 U/kg) and their combination. At the age of 42 days, the behavior of the rats was evaluated through 5 sensorimotor tests. Muscle power, motor coordination, reflexes and limb placing (LP) were tested to different sensory stimulations. The sensorimotor tests lasted six days. The study was completed with the evaluation of brain tissue damages at the age of 48 days. Results: In all the separate tests the HI rats performed significantly worse than the control and treated rats (table). In particular the differences between the groups in the grip traction, postural reflex and limb placing task were more pronounced compared to other tests (table). Neonatal HI resulted in extensive neuronal damage that was significantly limited after treatment. groups with different letter (a, b, c) differ significantly groups with different letter (a, b, c) differ significantly Conclusion: HI brain damage during the neonatal period resulted in long-term disorders in motor coordination, muscle power and the reaction of the limbs to sensory stimuli. EPO and NAC attenuated the effects of HI on the neonatal brain by reducing the progression of neuronal injury and improving sensorimotor function. However their combination resulted in more pronounced functional improvement. Behavioral alterations represent a useful endpoint for studying the consequences of a perinatal HI insult and the efficacy of potential neuroprotective treatments.