Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia

Front Biosci. 2007 Jan 1;12:2728-34. doi: 10.2741/2267.


Excessive poly(ADP-ribose) polymerase-1 (PARP-1) activation plays a significant role in ischemic brain damage. Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. Based on our in vitro finding that NAD+ treatment can abolish PARP-1-mediated cell death, we hypothesized that NAD+ administration may decrease ischemic brain injury. In this study, we used a rat model of transient focal ischemia to test this hypothesis. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains. Intranasal delivery with 10 mg/kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia. The NAD+ administration also significantly attenuated ischemia-induced neurological deficits. In contrast, intranasal administration with 10 mg/kg nicotinamide did not decrease ischemic brain damage. These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • Disease Models, Animal
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / pathology
  • Male
  • Myocardial Infarction / pathology
  • NAD / administration & dosage
  • NAD / therapeutic use*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Rats
  • Rats, Sprague-Dawley


  • Poly(ADP-ribose) Polymerase Inhibitors
  • NAD
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1