Altered susceptibility of the blood‐brain barrier to disruption in type 1 diabetes (685.2)

Abstract

Our previous studies have shown that nitric oxide synthase‐dependent responses of cerebral arterioles are impaired in Type 1 diabetic (T1D) rats by a mechanism that appears to involve an increase in oxidative stress. Since the integrity of the blood‐brain barrier (BBB) may be influenced by nitric oxide and oxidative stress, we reasoned that the susceptibility of the BBB to disruption may be altered by T1D as well. Thus, our goal was to examine basal and agonist‐induced changes in permeability of the BBB in nondiabetic and diabetic (streptozotocin; 50 mg/kg IP) rats. On the day of the experiment (2‐3 months after streptozotocin), a craniotomy was made over the parietal cortex. We measured the permeability of the BBB to FITC‐10K dextran in nondiabetic and diabetic rats under basal conditions and during topical application of histamine (eNOS‐dependent) or glutamate (nNOS‐dependent). In addition, we examined the levels of superoxide anion in brain tissue using lucigenin chemiluminescence. Finally, we measured tight junctional protein levels in brain tissue of nondiabetic and diabetic rats. We found that basal permeability of the BBB was increased in diabetic compared to nondiabetic rats. In addition, eNOS‐ and nNOS‐dependent changes in permeability of the BBB were less in diabetic compared to nondiabetic rats. Finally, tight junctional protein and superoxide anion levels were altered by T1D. We suggest that T1D can influence the susceptibility of the BBB to disruption by altering the balance between nitric oxide and superoxide anion. We speculate that altered permeability characteristics of the BBB may contribute to cognitive impairment/impaired neurovascular coupling observed in diabetic patients.Grant Funding Source: NIH HL090657