In vivo neuroprotection by a creatine-derived compound

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 MgSO4, 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 MgSO4 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