Clomethiazole protects against hemineglect in a primate model of stroke

Permanent occlusion of the M1 segment of the middle cerebral artery (pMCAO) in the marmoset, a New World species of monkey, produces unilateral functi onal deficits, including motor neglect with the contralesional arm and cont ralesional spatial hemineglect. In this study we examined whether clomethia zole, a drug which modulates the gamma-aminobutyric acid, receptor, reduced the severity of the hemineglect and other deficits in this primate model o f stroke. Nine monkeys received pMCAO; 1 h later four of the nine were admi nistered clomethiazole by intraperitoneal injection and subcutaneous implan tation of osmotic mini-pumps, which released clomethiazole for 48 h, The mo nkeys had been trained and tested on a number of behavioral tasks prior to surgery and were retested 3 and 10 weeks later. Three weeks after pMCAO, mo nkeys treated with clomethiazole had a significantly reduced degree of spat ial neglect compared to untreated controls. Clomethiazole was not effective against the severe contralesional motor impairment in the current study, a lthough it ameliorated a somewhat less severe motor deficit in a previous s tudy in which the more distal, M2 segment of the middle cerebral artery had been occluded, Postmortem analysis of the brains showed that clomethiazole treatment had significantly reduced the area of damage in part of the pari etal cortex. These data suggest that clomethiazole may reduce the neglect t hat can be a debilitating consequence of right-sided stroke in man. (C) 200 0 Elsevier Science Inc.