The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury.
Pyrroloquinoline quinone is a ubiquitous redox cofactor and putative essential nutrient in mammals. Pyrroloquinoline quinone has recently been demonstrated to depress N-methyl-D-asparate induced electrical responses and is neuroprotective in vitro. In addition, pyrroloquinoline quinone has been demonstrated to act as a free radical scavenger in mammalian tissues. In this study, we demonstrate a neuroprotective effect of pyrroloquinoline quinone in an in vivo cerebral hypoxia/ischemia model in the rodent. Significant reduction in infarct size resulted from pyrroloquinoline quinone pretreatment and also when pyrroloquinoline quinone was administered following induction of hypoxia/ischemia. The neuroprotective effect was not dependent on change in core or cranial temperatures, as there was no difference between temperature measurements in pyrroloquinoline quinone-treated and vehicle-treated controls. No changes in electroencephalographic activity were observed at neuroprotective doses. These findings suggest that pyrroloquinoline quinone may represent a novel class of quinoid reagents of potential use in the treatment of neurological disorders that involve excitotoxicity. This study demonstrates a protective effect of the novel essential nutrient pyrroloquinoline quinone on brain injury in a rodent model of cerebral hypoxia/ischemia. Pyrroloquinoline quinone was neuroprotective when administered before and even after the insult, and did not appear to have significant neurobehavioral side effects. Pyrroloquinoline quinone represents a new class of agents with potential use in the therapy of stroke.
Department of Neurology, Children's Hospital, Boston, MA.
F E
FE
Jensen
G J
GJ
Gardner
A P
AP
Williams
P M
PM
Gallop
E
E
Aizenman
P A
PA
Rosenberg
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D003067:Coenzymes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000503:physiopathology / Q000517:prevention & control*; D045542:PQQ Cofactor; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats
D003067:Coenzymes; D016166:Free Radical Scavengers; D015363:Quinolones; D045542:PQQ Cofactor