Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats

Baiba Svalbe, Liga Zvejniece, Edijs Vavers, Osvalds Pugovics, Ruta Muceniece, Edgars Liepinsh, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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 90. min, followed by the intraperitoneal administration of mildronate at doses of 100 and 200. mg/kg 2. h after reperfusion and then daily for an additional 14. days. 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 14. days post-stroke. Treatment with mildronate at a dose of 200. mg/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.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalBehavioural Brain Research
Volume222
Issue number1
DOIs
Publication statusPublished - 12 Sep 2011

Keywords*

  • Functional recovery
  • L-Carnitine
  • Mildronate
  • Stroke

Field of Science*

  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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