BDNF protects against spatial memory deficits following neonatal hypoxia-ischemia

Hypoxic-ischemic (H-I) brain injury in the human perinatal period often lea ds to significant long-term neurobehavioral dysfunction in the cognitive an d sensory-motor domains. Using a neonatal H-I injury model (unilateral caro tid ligation followed by hypoxia) in postnatal day seven rats, previous stu dies have shown that neurotrophins, such as brain-derived neurotrophic fact or (BDNF), can be protective against neural tissue loss. The present study explored potential relationships between neural protective and behavioral p rotective strategies in this neonatal H-I model by determining if neonatal H-I was associated with behavioral spatial learning and memory deficits and whether the neurotrophin BDNF was protective against both brain injury and spatial learning/memory dysfunction. Postnatal day seven rats received veh icle or BDNF pretreatments (intracerebroventricular injections) followed by H-I or sham treatments and then tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 20 to 30 , and their brains were histologically analyzed at 4 weeks following treatm ents. H-I rats with vehicle pretreatment displayed significant tissue loss in the hippocampus (including CA1 neurons), cortex, and striatum, as well a s severe spatial memory deficits (e.g., short probe times). BDNF pretreatme nt resulted in significant protection against both H-I-induced brain tissue losses and spatial memory impairments. These findings indicate that unilat eral H-I brain injury in a neonatal rodent model is associated with cogniti ve deficits, and that BDNF pretreatment is protective against both brain in jury and spatial memory impairment. (C) 2000 Academic Press.