Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures

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. (C) 2003 Elsevier Science B.V. All rights reserved.