Carnosine is neuroprotective against permanent focal cerebral ischemia in mice

Stroke. 2007 Nov;38(11):3023-31. doi: 10.1161/STROKEAHA.107.488502. Epub 2007 Oct 4.

Abstract

Background and purpose: Carnosine is a naturally occurring dipeptide with multiple neuroprotective properties. In addition, it is well tolerated in high doses with minimal side effects. The purposes of this study were to determine whether carnosine is neuroprotective in permanent focal cerebral ischemia and to determine potential mechanisms of neuroprotection.

Methods: We investigated the efficacy of carnosine in a mouse model of permanent focal cerebral ischemia. The effects of carnosine were investigated with respect to neuronal damage and infarct formation, endogenous antioxidant status, and matrix metalloproteinase activity.

Results: Carnosine significantly decreased infarct size and neuronal damage when administered at time points both before and after the induction of ischemia. Carnosine also decreased reactive oxygen species levels in the ischemic brain, preserved normal glutathione levels, and decreased matrix metalloproteinase protein levels and activity.

Conclusions: Carnosine is neuroprotective in focal cerebral ischemia and appears to influence deleterious pathological processes that are activated after the onset of ischemia.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Carnosine / metabolism
  • Carnosine / pharmacology*
  • Carnosine / therapeutic use
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / physiopathology
  • Cerebral Infarction / prevention & control
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Glutathione / agonists
  • Glutathione / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Matrix Metalloproteinase Inhibitors
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Carnosine
  • Matrix Metalloproteinases
  • Glutathione