BDNF protects against spatial memory deficits following neonatal hypoxia-ischemia

Exp Neurol. 2000 Nov;166(1):99-114. doi: 10.1006/exnr.2000.7492.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn / physiology*
  • Asphyxia Neonatorum / drug therapy*
  • Asphyxia Neonatorum / pathology
  • Asphyxia Neonatorum / physiopathology
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Brain Injuries / drug therapy
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cell Count
  • Disease Models, Animal
  • Female
  • Humans
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / physiopathology
  • Infant, Newborn
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / drug therapy*
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Pregnancy
  • Rats
  • Recovery of Function / drug effects
  • Recovery of Function / physiology


  • Brain-Derived Neurotrophic Factor