TY - JOUR
T1 - Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats
AU - Svalbe, Baiba
AU - Zvejniece, Liga
AU - Vavers, Edijs
AU - Pugovics, Osvalds
AU - Muceniece, Ruta
AU - Liepinsh, Edgars
AU - Dambrova, Maija
N1 - Funding Information:
This study was supported by the Latvian State Research Program grant No. 2010.10-4/VPP-4 and the European Social Fund project Nr. 2009/0138/1DP/1.1.2.1.2/09/IPIA/VIAA/004.
PY - 2011/9/12
Y1 - 2011/9/12
N2 - 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.
AB - 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.
KW - Functional recovery
KW - L-Carnitine
KW - Mildronate
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=79953717427&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2011.03.027
DO - 10.1016/j.bbr.2011.03.027
M3 - Article
C2 - 21420440
AN - SCOPUS:79953717427
SN - 0166-4328
VL - 222
SP - 26
EP - 32
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -