Structural and functional recovery elicited by combined putrescine and aminoguanidine treatment after aspirative lesion of the fimbria–fornix and overlying cortex in the adult rat

Abstract

Damage to the adult CNS often causes permanent deficits. Based on a lesion model of septohippocampal pathway aspiration in the rat, we attempted to promote neuronal cell survival and post-traumatic recovery by using a pharmacological treatment combining aminoguanidine and putrescine (AGP). The functional recovery was followed over 15 weeks before morphological analysis. AGP treatment produced a persistent attenuation (approximately 50%) of the lesion-induced hyperactivity, a reduction (approximately 60%) in the sensorimotor impairments and an improved performance in the water-maze task which did not, however, rely upon improved memory capabilities. AGP weakened the lesion-induced decrease in ChAT-positive neurons in the medial septum and the extent of thalamic retrograde necrosis (by approximately 30% in each case) and resulted in a partial cholinergic reinnervation of the dentate gyrus. These promising results support the idea that coadministration of putrescine and aminoguanidine might become a potent way to foster structural and functional recovery (or compensation) in the adult mammalian CNS after injury.