Objective: To explore the mechanism of the changes of blood-cerebrospinal fluid barrier in rabbits with diabetic ketoacidosis (DKA).
Methods: The New Zealand rabbits were injected with 150 mg/kg streptozotion and alloxan monohydrate each (model group, n=6) intravenously, or equal volume of normal saline (control group, n=6). After 72 hours, blood sugar and uric ketone were detected. All of animals were injected with Evans blue (EB). After 6 hours, arterial blood gases were measured and animals were killed. Absorbency of EB of brain tissue was detected. All brains of animals were examined with light and electron microscopy. Marker of blood-cerebrospinal fluid barrier, cytochemical stains of alkaline phosphatase (ALPase) was operated by ultrastructure. The inducible nitric oxide synthase (iNOS) in brain tissue was detected by immunohistochemical method.
Results: The models of DKA were established after 72 hours of injecting streptozotion and alloxan monohydrate. Absorbency of EB of model group rabbits was slightly increased, but had no significant difference compared with controls (P>0.05). The brain edema, damages of vessel endothelium and necrosis of neuron were observed through histological and ultrastructure examination in model group. ALPase activity of model group was evidently decreased in brain blood vessel endothelium in comparison with controls. Compared to controls, the iNOS activity of model group was increased and its positive cells were aggregated on blood vessel of brain membrane.
Conclusion: By streptozotion and alloxan monohydrate inducing DKA models, NO could induce blood-cerebrospinal fluid barrier damages and result in brain edema.