BDNF protects against spatial memory deficits following neonatal hypoxia-ischemia

C. Robert Almli, Todd J. Levy, Byung Hee Han, Aarti R. Shah, Jeffrey M. Gidday, David M. Holtzman

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Hypoxic-ischemic (H-I) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal H-I injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, previous studies have shown that neurotrophins, such as brain-derived neurotrophic factor (BDNF), can be protective against neural tissue loss. The present study explored potential relationships between neural protective and behavioral protective 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 vehicle 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 treatments. H-I rats with vehicle pretreatment displayed significant tissue loss in the hippocampus (including CA1 neurons), cortex, and striatum, as well as severe spatial memory deficits (e.g., short probe times). BDNF pretreatment resulted in significant protection against both H-I-induced brain tissue losses and spatial memory impairments. These findings indicate that unilateral H-I brain injury in a neonatal rodent model is associated with cognitive deficits, and that BDNF pretreatment is protective against both brain injury and spatial memory impairment. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)99-114
Number of pages16
JournalExperimental Neurology
Volume166
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Brain-derived neurotrophic factor (BDNF)
  • CA1 neurons
  • Cortex
  • Hippocampus
  • Hypoxia-ischemia
  • Place navigation
  • Spatial memory
  • Striatum
  • Water maze

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