In vivo neuroprotection by a creatine-derived compound: phosphocreatine-Mg-complex acetate.

Abstract

Phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) is a creatine-derived compound that in previous in vitro research was able to increase neuronal creatine independently of the creatine transporter, thus providing hope to cure the hereditary syndrome of creatine transporter deficiency. In previous research we showed that it reproduces in vitro the known neuroprotective effect of creatine against anoxic damage. In the present paper we investigated if PCr-Mg-CPLX reproduces this neuroprotective effect in vivo, too. We used a mouse model of transient middle cerebral artery occlusion. Mice received PCr-Mg-CPLX or a mixture of the two separate compounds phosphocreatine (PCr) and MgSO(4), or vehicle. The injections were done 60 min and 30 min before ischemia. Forty-eight hours after ischemia neurological damage was evaluated with Clark's behavioural tests, then the infarct volume was measured. PCr-Mg-CPLX reduced the infarct volume by 48%, an effect that was not duplicated by the separate administration of PCr and MgSO(4) and the neurological damage was decreased in a statistically significant way. We conclude that PCr-Mg-CPLX affords in vivo neuroprotection when administered before ischemia. These results are comparable to previous research on creatine administration in experimental stroke. PCr-Mg-CPLX maintains creatine-like neuroprotective effects in vivo as well as in vitro. Our study suggests that PCr-Mg-CPLX might have a therapeutic role in the treatment of hereditary creatine transporter deficiency and of conditions where there is a high risk of impending stroke or cerebral ischemic damage, like high-risk transient ischemic attacks, open heart surgery, and carotid surgery.

• Authors: L Perasso, E Adriano, P Ruggeri, S V Burov, C Gandolfo, M Balestrino
• Journal: Brain research (Brain Res) Vol. 1285 Pg. 158-63 (Aug 18 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19523930 (Publication Type: Journal Article)

Chemical References

• Membrane Transport Proteins
• Neuroprotective Agents
• creatine transporter
• Phosphocreatine
• Magnesium
• Creatine

Topics

• Animals
• Brain Infarction (drug therapy, physiopathology, prevention & control)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Creatine (metabolism)
• Cytoprotection (drug effects, physiology)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, physiopathology)
• Magnesium
• Male
• Membrane Transport Proteins (deficiency, drug effects)
• Mice
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphocreatine (analogs & derivatives, pharmacology, therapeutic use)
• Treatment Outcome