Abstract
The blood-brain barrier (BBB) can be opened transiently by infusing a hyperosmolal solution of a non-electrolyte into the internal carotid artery. We investigated the hypothesis that capillary polyamines and their rate-regulating synthetic enzyme, ornithine decarboxylase (ODC), may be involved in mediating BBB breakdown in this model, as they are in BBB breakdown by focal cold injury. The intracarotid infusion of 1.6 M mannitol induced a prompt (less than 2 min) increase in ODC activity and the levels of polyamines in the ipsilateral hemisphere. Isolated cerebral capillary preparations and neural elements showed similar increases in ODC activity. The rank order of increase at 2 min, ODC (170%) greater than putrescine (90%) greater than spermidine (15%) greater than spermine (7%), was consistent with an activation of the ODC-regulated pathway of polyamine synthesis. The specific ODC inhibitor alpha-difluoromethylornithine (DFMO) blocked the 1.6 M mannitol-induced increase in ODC activity and the accumulation of polyamines, and concurrently prevented BBB breakdown, monitored by transport of intravenously administered Evans blue and alpha-[3H]aminoisobutyrate into cerebral tissue. Exogenous putrescine, the product of ODC activity,...Continue Reading
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