Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat

Brain Res. 2006 Jun 13;1094(1):200-6. doi: 10.1016/j.brainres.2006.03.111. Epub 2006 May 18.

Abstract

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. It has previously been reported to reduce infarct size in 7-day-old rat pups with an in vivo cerebral hypoxia/ischemia model (Jensen et al., 1994). In this study, we tested whether improvement is found in both behavioral measures of protection and by histological measures of infarcted tissue at 72 h after reversible middle cerebral artery occlusion (rMCAo) in adult rats. Two-hour rMCAo was induced in adult rats using the intraluminal suture technique. PQQ (10, 3, and 1 mg/kg) was given once by intravenous injection at the initiation, or 3 h after the initiation, of 2 h rMCAo. Neurobehavioral deficits were evaluated daily for 3 days followed by infarct volumes measurements by 2,3,5-triphenyltetrazolium chloride (TTC) staining. PQQ at 10 mg/kg infused at the initiation, or 3 h after the initiation, of rMCAo was effective in reducing cerebral infarct volumes measured 72 h later. At 3 h after ischemia, a dose of 3 mg/kg significantly reduced infarct volume compared to vehicle-treated animals, but 1 mg/kg was ineffective. Neurobehavioral scores were also significantly better in the PQQ-treated group compared to the vehicle controls when PQQ was given at 10 and 3 mg/kg, but not at 1 mg/kg. Thus, PQQ is neuroprotective when given as a single administration at least 3 h after initiation of rMCAo. These data indicate that PQQ may be a useful neuroprotectant in stroke therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain / blood supply
  • Brain / drug effects
  • Brain / physiopathology
  • Brain Infarction / drug therapy*
  • Brain Infarction / physiopathology
  • Brain Infarction / prevention & control
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / physiopathology
  • Male
  • Molecular Structure
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control
  • Neurons / drug effects
  • Neurons / physiology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • PQQ Cofactor / chemistry
  • PQQ Cofactor / pharmacology*
  • PQQ Cofactor / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Time Factors

Substances

  • Neuroprotective Agents
  • PQQ Cofactor