Though diabetes is a disease with vascular complications, little is known about its effects on the blood-brain barrier or the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is situated at choroid plexuses located in the lateral, third, and fourth ventricles. Choroid plexuses are the primary site of cerebrospinal fluid (CSF) production and express numerous ion transporters. Previous studies have shown a perturbation of ion transport in the periphery and brain during diabetes. In this study, we investigated the effect of diabetes on ion transporters in the choroid plexuses of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of STZ (60 mg/kg in citrate buffer, confirmed by glucose analysis: 601 ؎ 22 mg/dl diabetic rats, 181 ؎ 46 mg/dl age-matched controls); and at 28 days, rats were killed, choroid plexuses harvested, and protein extracted. Western blot analyses were carried out using antibodies for ion transporters, including Na ؉ -K ؉ -2Cl ؊ cotransporter and the Na iabetes is a disease with numerous vascular complications. Previous studies have shown perturbations in ion transport in both the periphery and the brain during diabetes (1-3). Though diabetes is a vascular disease, little is known regarding the effects of diabetes on the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB). It has been reported that diabetes is a risk factor not only for stroke (4,5), but also for normal-pressure hydrocephalus (6,7). Hydrocephalus is caused by excessive retention or production of cerebrospinal fluid (CSF) within the central nervous system. CSF is produced by the choroidal epithelial cells of the choroid plexus (8). The choroid plexuses are also the site of the BCSFB and are located in the lateral, third, and fourth ventricles. Capillaries of the choroid plexus are fenestrated, allowing extracellular fluid formation (unlike other brain capillary beds). CSF production involves the combination of a number of transport systems in the choroid plexus (9) (Fig. 1).Animal models of diabetes have shown that the Na (13), and Na ϩ -K ϩ -ATPase (14 -17) have altered expression and activity in a number of vascular beds. These three transporters are critical for CSF production and pH maintenance (9). In this study, we have investigated the effects of the streptozotocin (STZ) model of type 1 diabetes on expression of the Na ϩ -H ϩ exchanger, NaϪ cotransporter, and Na ϩ -K ϩ -ATPase in the rat choroid plexus.
RESEARCH DESIGN AND METHODS
Induction of diabetes.All protocols used in this study were approved by the University of Arizona Institutional Animal Care and Use Committee and abide by National Institutes of Health guidelines. Diabetes was induced in male 300-to 325-g Sprague-Dawley rats (Harlan, Indianapolis, IN) via an intraperitoneal injection of 60 mg/kg STZ (Sigma, St. Louis, MO) in sterile phosphate buffered saline. Control animals were injected intraperitoneally with phosphate buffered saline. The animals were housed under ...