Mildronate (3-(2,2,2-trimethylhydrazinium) propionate) is an inhibitor of
l-carnitine biosynthesis and an anti-ischemic
drug. In the present study, we investigated the effects of
mildronate in rats following focal
cerebral ischemia. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90min, followed by the intraperitoneal administration of
mildronate at doses of 100 and 200mg/kg 2h after reperfusion and then daily for an additional 14days. The beam-walking, rota-rod and cylinder tests were used to assess sensorimotor function, and vibrissae-evoked forelimb-placing and limb-placing tests examined responses to tactile and proprioceptive stimulation. Following behavioural testing, the
infarct volume was measured. The cerebellar concentrations of
l-carnitine, γ-
butyrobetaine (GBB) and
mildronate were also measured. The results showed that saline-treated MCAO rats had minor or no spontaneous recovery in sensorimotor and proprioceptive function up to 14days post-
stroke. Treatment with
mildronate at a dose of 200mg/kg was found to accelerate recovery of motor and proprioceptive deficits in limb-placing, cylinder and beam-walking tests. Analysis of rat cerebellar
tissue extracts revealed that
l-carnitine and GBB concentrations changed with
mildronate treatment; the concentration of
l-carnitine was significantly decreased by
mildronate treatment, whereas the concentration of GBB was significantly increased. Cerebellar concentrations of
mildronate also increased in a dose-dependent manner following systemic administration.
Infarct size did not differ among the experimental groups on post-
stroke day 14. The present study suggests that
mildronate treatment improves the functional outcome in MCAO rats without influencing
infarct size.