After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This "time of aggregation" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect.

Background: Peripheral neuropathy of both motor and sensory nerves has been well documented in diabetes mellitus, but the evidence for physiological and correlated morphological changes during the pathogenesis of myopa-thy is scarce. In the present report, we have chosen the dorsiflexor muscle of adult male mice as a model for studying in situ muscle contraction and neuromuscular ultrastructure during the pathogenesis of streptozotocin-induced diabetes. Methods: Thirty mice (30 g bodyweight) were injected once i.p. with streptozotocin solution (200 mg/kg) to induce experimental diabetes mellitus. Comparative analyses of in situ muscle isometric contractile characteristics were studied (at 1 Hz, 5 Hz, and 30 Hz nerve stimulation) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and 8 weeks postinjection. Synaptic delay was also recorded in diabetic and age-matched control mice. Results: There was a significant increase in synaptic delay in both 4-week and 8-week diabetic mice compared with control mice (8.9 1.2 msec and 7.6 0.6 msec, respectively, compared with 6.

The hydroxyl radical scavengers dimethyl sulfoxide (DMSO) and glycerol were effective inhibitors of platelet aggregation in an in vivo mouse model of pial arteriolar injury. Aggregability was expressed in terms of the time required for a noxious stimulus (light + dye) to initiate aggregation. These drugs, given 1 hour before the injury, also eliminated the dilation which accompanied the damage. The same drugs failed to influence the constriction which accompanied an identical injury to mouse mesenteric arterioles, but again impaired platelet aggregation in the damaged mesenteric vessel. The data support the concept recently introduced by others, that, in the brain, hydroxyl radicals may mediate vascular damage and/or dilation accompanying the damage. The data also support the concept platelet aggregation may be stimulated, directly or indirectly, by hydroxyl radical. The effects of DMSO and glycerol in this study, irrespective of the molecular basis for the effects, may be relevant to the reported therapeutic benefit of these agents in cerebrovascular disease.

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