Characterization of long-term functional outcome in a murine model of mild brain ischemia

被引:95
作者
Balkaya, Mustafa [1 ]
Kroeber, Jan [1 ,2 ]
Gertz, Karen [1 ,2 ]
Peruzzaro, Sarah [1 ]
Endres, Matthias [1 ,2 ,3 ]
机构
[1] Charite, Klin Hsch Ambulanz Neurol, D-10117 Berlin, Germany
[2] Charite, Ctr Stroke Res Berlin, D-10117 Berlin, Germany
[3] Charite, Ctr Excellence Neurocure, D-10117 Berlin, Germany
关键词
Mild brain ischemia; Middle cerebral artery occlusion; Long-term functional outcome; Behavioral characterization; MIDDLE CEREBRAL-ARTERY; ADHESIVE REMOVAL TEST; ENVIRONMENTAL ENRICHMENT; STROKE RESEARCH; AGED RATS; MOUSE; MICE; OCCLUSION; DEFICITS; NEUROPROTECTION;
D O I
10.1016/j.jneumeth.2012.12.021
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Evaluation of functional outcome over the course of several weeks after ischemia is a key component in improving the clinical relevance of experimental stroke studies. Using a battery of behavioral tests, we characterized functional outcome in mice over 4 weeks following 30 min of proximal middle cerebral artery occlusion (MCAo). We evaluated rotarod, chimney, pole and cylinder tests to assess short term functional deficits in a transient stroke model which induces infarcts mainly in the striatum. The corner test, adhesive removal test, cylinder test, catwalk, paw preference test and novel tests of rotation were evaluated for long-term functional outcome. Rotarod detected deficits within the first week and pole test was reliable up to intermediate time points after MCAo. Corner test, adhesive removal test, catwalk and paw preference test detected deficits for up to 4 weeks, as did the novel corner rotation and bowl tests. Chimney and cylinder test did not prove useful in our model of mild stroke. In summary, we established the pole test and rotarod as useful tools to evaluate sensory motor deficits early after mild stroke, and corner test and adhesive removal test at later time-points. Alternatively, corner rotation may be a suitable test of long-term function. Test batteries may be further complemented by catwalk and paw preference test for clinically relevant deficits. There was no correlation of behavioral outcome with lesion size at 28 days, and determining whether these tests are useful for detecting a potential benefit of neuroprotective or regenerative therapies requires further testing. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:179 / 187
页数:9
相关论文
共 28 条
[1]   TURNING BEHAVIOR INDUCED BY ELECTRICAL-STIMULATION OF NIGRO-NEOSTRIATAL SYSTEM OF RAT [J].
ARBUTHNOTT, GW ;
UNGERSTEDT, U .
EXPERIMENTAL NEUROLOGY, 1975, 47 (01) :162-172
[2]  
Balkaya M, 2010, NEUROMETHODS, V47, P179, DOI 10.1007/978-1-60761-750-1_13
[3]   Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse [J].
Bouet, Valentine ;
Freret, Thomas ;
Toutain, Jerome ;
Divoux, Didier ;
Boulouard, Michel ;
Schumann-Bard, Pascale .
EXPERIMENTAL NEUROLOGY, 2007, 203 (02) :555-567
[4]   The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice [J].
Bouet, Valentine ;
Boulouard, Michel ;
Toutain, Jerome ;
Divoux, Didier ;
Bernaudin, Myriam ;
Schumann-Bard, Pascale ;
Freret, Thomas .
NATURE PROTOCOLS, 2009, 4 (10) :1560-1564
[5]  
Buchhold B, 2007, RESTOR NEUROL NEUROS, V25, P467
[6]   ON INHERITANCE OF HANDEDNESS .I. LATERALITY IN INBRED MICE [J].
COLLINS, RL .
JOURNAL OF HEREDITY, 1968, 59 (01) :9-&
[7]   International, multicenter randomized preclinical trials in translational stroke research: It's time to act [J].
Dirnagl, Ulrich ;
Fisher, Marc .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2012, 32 (06) :933-935
[8]   Long-term behavioral assessment of function in an experimental model for ischemic stroke [J].
Encarnacion, Angelo ;
Horie, Nobutaka ;
Keren-Gill, Hadar ;
Bliss, Tonya M. ;
Steinberg, Gary K. ;
Shamloo, Mehrdad .
JOURNAL OF NEUROSCIENCE METHODS, 2011, 196 (02) :247-257
[9]   Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family [J].
Endres, H ;
Namura, S ;
Skimizu-Sasamata, M ;
Waeber, C ;
Zhang, L ;
Gómez-Isla, T ;
Hyman, BT ;
Moskowitz, MA .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1998, 18 (03) :238-247
[10]   Improving outcome after stroke: Overcoming the translational roadblock [J].
Endres, Matthias ;
Engelhardt, Britta ;
Koistinaho, Jari ;
Lindvall, Olle ;
Meairs, Stephen ;
Mohr, Jay P. ;
Planas, Anna ;
Rothwell, Nancy ;
Schwaninger, Markus ;
Schwab, Martin E. ;
Vivien, Denis ;
Wieloch, Tadeusz ;
Dirnagl, Ulrich .
CEREBROVASCULAR DISEASES, 2008, 25 (03) :268-278