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Spatio-temporal Properties Of Locomotor Activity Within 24 Hours After Focal Cerebral Ischemia In Mice

Posted on:2005-04-09Degree:MasterType:Thesis
Country:ChinaCandidate:Q ZhangFull Text:PDF
GTID:2144360122981192Subject:Pharmacology
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Locomotor activity is the most basic behavioral phenomenon of animals, and can be used in many kinds of psychoneuropharmacological investigations. There have been many studies on the space characteristics in short-duration and the characteristics of day and night activity. However, the long-time continuous observations of locomotor activity in free and wakeful animals are still lack. The distance of locomotor activity has been determined quantitatively in limited durations in some studies, and the results are not consistent. Locomotor activity would be changed after focal cerebral ischemia because of hemiplegia. Up to date, passive behavior assessments are most commonly used to observe the neurological deficiency of focal cerebral ischemic animals, but active behavioral properties, especially locomotor activities, are rarely used. Further investigations are still needed on spatio-temporal properties of animal locomotor activity.The purposes of this study were to (1) develop a new method for evaluating the long-time locomotor activity of mice in a open field by a video-tracking system; (2) elucidate the spatio-temporal properties of locomotor activity in mice; (3) observe the changes of locomotor activity after focal cerebral ischemia and the usefulness of these changes as quantitative variables for objectively evaluating neurological dysfunction after ischemia; and (4) investigate the effect of pranlukast { ONO-1078, 4-oxo-8-[p-(4-phenylbutyloxy)benzoyl- amino]-2-(tetrazol-5-yl)-4H-l-benzopyran hemihydrate}, a neuroprotective agent, on properties of locomotor activity after focal cerebral ischemia in mice.In this study, permanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) using intraluminal suture in mice. The open field locomotor activity of animals was recorded from 2 h to 24 h after the operation using a video-tracking system. The open field was divided into central, home and peripheral zones arbitrarily. Bederson neurological scores and the holding angles were determined to evaluate the neurological function 24 h after ischemia, then the mice were perfused and fixed with 4% paraformaldehyde and the brains were removed. Coronal cryostat sections (8 urn and 20 m) were prepared from bregma -2.0 mm, and stained with Toluidine blue. The 8 um brain sections were used for observe pathological changes under light microscope, and the images were stored in the computer. The survived neuron densities in hippocampal CA1 region, temporal cortex and subcortex was countered. The 20 um brain sections were photographed using a digital camera, and the infarct area was calculated using MedBrain 2 imaging analyzer. The drug-treated mice were ip injected with pranlukast (0.1 mg/kg) once a day for consecutive 3 days and 30 min before surgery. The ischemia control and sham operation mice were ip injected with saline (10 ml/kg) at the same time points.We found that the sham operation mice moved in the open field in a linear pattern, but the ischemic mice with a circular pattern throughout the 22 h observation (from 2 h to 24 h after ischemia). There was no significant difference in the total moving distance in 22 h between the two groups. But there were significant differences of the distance and the spent time in different zones between two groups (P < 0.001), as indicated by the ratios of distance and time in different zones. The locomotor activity of sham operation mice presented obvious regional properties. These normal mice preferred to stay in home base (the food and water zones), and frequently visited the peripheral zones (more frequently in the other two comers) but few the center zones. However, ischemic mice lost such regional properties, and there were no significant differences of distance and time in each zone. Pranlukast (0.1 mg/kg) did not alter the changes of locomotor activity significantly after ischemia. All the mice were most active within the first 1 h, and then decreased.Ischemic mice showed neurological deficiency and decreased holding angles 24 h after M...
Keywords/Search Tags:Focal cerebral ischemia, Locomotor activity, Mouse, Behavior, Open field, Home base, Pranlukast {4-oxo-8-[p-(4-phenylbutyloxy)benzoyl-amino]-2-(tetrazol-5-yl)-4H-l-benzopyran hemihydrate}
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