Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: Evidence for a preconditioning mechanism

Stroke, an age-related disorder involving degeneration of neurons resulting from cerebral ischemia, is a major cause of disability and mortality. Alth ough dietary restriction (DR) extends lifespan and reduces levels of cellul ar oxidative stress in several different organ. systems including the brain , the impact of DR on ischemic brain injury is unknown,We report that maint enance of adult rats on a DR regimen resulted in reduced brain damage and i mproved behavioral outcome in a middle cerebral artery occlusion-reperfusio n (MCAO-R) stroke model. Administration of 2-deoxyglucose (2-DG), a nonmeta lbolizable analogue of glucose, to rats fed ad libitum resulted in reduced ischemic brain damage and improved behavioral outcome following MCAO-R, 2-D G protected cultured hippocampal neurons against chemical hypoxia, demonstr ating a direct protective action on neurons. DR and 2-DG administration res ulted in an increase in the level of the stress protein heat-shock protein 70 (HSP-70) in striatal cells in vivo, and 2-DG treatment induced HSP-70 in cultured neurons suggesting involvement of a preconditioning stress respon se in the neuroprotective actions of De and 2-DG, The neuroprotective effec t of DR and 2-DG in this focal cerebral ischemia model suggests that outcom e following stroke may be improved in individuals who follow a regimen of r educed food intake. (C) 1999 Wiley-Liss, Inc.