title: Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures.
abstract: Three experimental neuroprotective agents (clomethiazole, AR-R15896AR and NXY-059) have recently been tested in a primate model of acute ischaemic stroke. As the experimental techniques used in all three studies were similar and the compounds were administered at clinically relevant doses, a comparative analysis of the functional benefits of these drug-treatments has now been performed. Furthermore a more detailed histological analysis of the neuroprotection afforded by the drugs has also been made. NXY-059 produced almost twice the degree of neuroprotection than that seen following clomethiazole or AR-R15896AR. Protection by NXY-059 was seen in measurements of damage to cortex and white matter. Clomethiazole and AR-R15896AR provided less protection of cortex and white matter than NXY-059. Conspicuously, AR-R15896AR was without effect in sub-cortical regions. NXY-059 was the only compound to produce a major, statistically significant improvement in the motor deficit induced by the stroke. All three drugs also reduced the degree of spatial neglect 3 weeks after pMCAO, and 10 weeks later only NXY-059 still provided significant additional functional benefit to the spontaneous improvement seen in stroked control animals not receiving treatment. The overview of the behavioural effects and these new histological findings suggest that NXY-059 was by far the most effective neuroprotective agent of the three examined.
authors.affiliation: MRC Comparative Cognition Team, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. jwbm2@cus.cam.ac.uk
authors.forename: Jonathan W B
authors.initials: JW
authors.lastname: Marshall
authors.forename: A Richard
authors.initials: AR
authors.lastname: Green
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Ridley
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001557:Benzenesulfonates; D002144:Callithrix; D002540:Cerebral Cortex / Q000473:pathology; D002719:Chlormethiazole / Q000097:blood / Q000627:therapeutic use; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005069:Evaluation Studies as Topic; D005108:Extinction, Psychological / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000473:pathology; D018696:Neuroprotective Agents / Q000097:blood / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000097:blood / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000627:therapeutic use; D013028:Space Perception / Q000187:drug effects; D013238:Stereotaxic Techniques; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D001557:Benzenesulfonates; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D011725:Pyridines; C096406:alpha-phenyl-2-pyridineethanamine dihydrochloride; D002719:Chlormethiazole; C120851:disufenton sodium