Local and remote microvascular changes in excitotoxin-induced focal brain lesions

We have examined the changes in the microvascular diameter, number/mm2 (NA) and area (AAi%) which occur after local brain lesions by the excitotoxin ibotenic acid (IBO). Rats (n = 18) were anesthetized with halothane. IBO (10 micrograms in 1 microliters of phosphate buffer) or vehicle was microinjected in a target region of the parietal cortex via glass micropipettes stereotaxically placed and animals were allowed to recover. Four 9, 15 and 30 days later rats were sacrificed and their brains removed, sectioned (thickness: 20 microns) and processed for the microvascular marker alkaline phosphatase. AAi%, NA and diameter were measured in the area of the lesion and in the homotopic contralateral cortical area by computer-assisted image analysis. In the lesion, AAi% increased by 83% at day 4, reached its maximum at day 9 (+227%) and then declined. Vascular diameter and NA also increased. However while diameter peaked at day 9 (+75%), Na reached its maximum at day 15 (+50%), at a time when AAi% was declining. In the contralateral cortex diameter increased at day 9 (+21%) but NA decreased (-35%) resulting in unchanged vascular area. Thus, focal brain lesions by excitotoxins produce substantial local and remote microvascular changes which have different patterns and may be mediated by distinct cellular and molecular mechanisms.