Isolated cerebral capillaries

Isolated capillaries have been used for a long time to study transport and metabolic function of the blood-brain barrier [61, 72, 75, 76, 78, 87-91], In contrast to monolayer cell cultures, which are susceptible to induction or inhibition of carrier protein expression, experiments with freshly isolated capillaries directly reflect the situation at the luminal side of brain capillaries. 

Capillaries can easily be isolated from whole brain, cutting brain tissue into little pieces, suspending them in buffer solution in a petri dish, and dissecting them with fine forceps. Capillary fragments can be found adhering to the glass bottom of the dish. 

Such studies are not limited to studying the interaction of potential substrates with ABC-transport proteins at the luminal membrane of brain capillaries but can also be used to investigate the regulatory mechanisms underlying the expression and function of these proteins as discussed above [72, 75, 78], 

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Tissue Location and Role of Aldose Reductase in Animal Models of Diabetic Complications. Aldose reductase (AR) has been located immunohistochemically in many tissues of the dog and rat, most notably, in corneal epithelium, retina, optic nerve, kidney papillae, aortic endothelium and smooth muscle cells as well as peripheral nerve and lens. AR has also been measured in human and monkey retinal mural cells. These cells are thought to provide the structural support for retinal capillaries and their loss is the first abnormality seen in clinical diabetic retinopathy. In addition, AR-like activity has been reported in a human retinoblastoma cell line and sorbinil inhibits this activity in these cells. Finally, a recent report has demonstrated that AR is present in isolated capillaries from bovine retina and cerebral cortex. Therefore, AR appears to be present in all tissues which are uniquely susceptible to deterioration during prolonged exposure to the hyperglycemia of diabetes. Accumulation of the products of the polyol pathway, sorbitol and fructose, has been demonstrated in these tissues and, where tested, sorbinil and other AR inhibitors have been shown to inhibit this accumulation. 

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