Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: Tests for long-term assessment.
In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits, especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study, we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to two months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington's and Parkinson's disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of middle cerebral artery occlusion (30 min) and were imaged 24 h later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24 h, seven days, and one and two months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine-induced rotations were the most reliable for assessing long-term deficits in the 30 min transient middle cerebral artery occlusion model of stroke.
1 School of Life Sciences, University of Nottingham, Nottingham, UK.
Rebecca C
RC
Trueman
2 Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK.
Claris
C
Diaz
1 School of Life Sciences, University of Nottingham, Nottingham, UK.
Tracy D
TD
Farr
2 Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK.
David J
DJ
Harrison
3 Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Anna
A
Fuller
4 Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, UK.
Paweł F
PF
Tokarczuk
5 EMRIC, Biosciences, Cardiff University, Cardiff, UK.
Andrew J
AJ
Stewart
6 PETIC, School of Medicine, Cardiff University, Cardiff, UK.
Stephen J
SJ
Paisey
2 Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK.
Stephen B
SB
Dunnett
D000818:Animals; D000067289:Behavior Observation Techniques / Q000379:methods*; D001522:Behavior, Animal; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D017208:Rats, Wistar; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000523:psychology*
Animal models; MCAO; behaviour (rodent); brain recovery; focal ischemia; immunohistochemistry; stroke