A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice

J Pharmacol Exp Ther. 2001 Jan;296(1):57-63.

Abstract

Brain injury induces disruption of the blood-brain barrier, edema, and release of autodestructive factors that produce delayed neuronal damage. NAPSVIPQ (NAP), a femtomolar-acting peptide, is shown to be neuroprotective in a mouse model of closed head injury. NAP injection after injury reduced mortality and facilitated neurobehavioral recovery (P < 0.005). Edema was reduced by 70% in the NAP-treated mice (P < 0.01). Furthermore, in vivo magnetic resonance imaging demonstrated significant brain-tissue recovery in the NAP-treated animals. NAP treatment decreased tumor necrosis factor-alpha levels in the injured brain and was shown to protect pheochromocytoma (PC12 cells) against tumor necrosis factor-alpha-induced toxicity. Thus, NAP provides significant amelioration from the complex array of injuries elicited by head trauma.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Head Injuries, Closed / drug therapy*
  • Head Injuries, Closed / mortality
  • Head Injuries, Closed / psychology
  • Homeodomain Proteins*
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred Strains
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / therapeutic use*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use*
  • PC12 Cells
  • Peptides / metabolism
  • Peptides / therapeutic use*
  • Postural Balance / drug effects
  • Rats
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / toxicity

Substances

  • Adnp protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Peptides
  • Tumor Necrosis Factor-alpha