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.
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.
Muller
Christophe
C
Laboratoire de Neurosciences Comportementales et Cognitives, LINC UMR 7191, GDR 2905 CNRS, IFR 37, 67000 Strasbourg, France.
Herberth
Heike
H
Cosquer
Brigitte
B
Kelche
Christian
C
Cassel
Jean-Christophe
JC
Schimchowitsch
Sarah
S
D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020712:Fornix, Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011700:Putrescine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006146:Guanidines; C004479:pimagedine; D011700:Putrescine