Islet Transplantation in a Subarachnoid Cavity Surrounding Olfactory Bulb of Diabetic Rats

Abstract

K.B. participated in making the research design, performing the research, analyzing the data, and writing the paper. A.V. participated in making the research design, performing the research, and analyzing the data. P.V. participated in making the research design and writing the paper.

Insulin delivery to the brain using intracranial implantation of alginate-encapsulated pancreatic islets

“…In our experiments, the amount of intracranially implanted islets corresponds to only 1.5–2.5% of the total number of transplanted islets usually required to achieve normoglycaemia in diabetic rats (Bloch et al, ; Ludwig et al, ). A persistent deficit of donor pancreas is one of the main clinical limitations of islet transplantation for treatment of type 1 diabetes in humans.…”

“…At low glucose concentration, islets release a small amount of insulin (basal insulin release) every few minutes, while elevated postprandial glucose concentrations increase insulin secretion (Hellman, ). Recently, we have shown that pancreatic islets transplanted in subarachnoid cavity of diabetic Lewis rats induced normoglycaemia in a metabolically regulated manner (Bloch et al, ). We suggest that a similar metabolic pattern of insulin secretion from implanted alginate‐encapsulated islets can elevate brain insulin content, which in turn, in the insulin‐related brain disorders, will be able to overcome brain insulin resistance/deficiency and ameliorate cognitive dysfunctions.…”

“…The immuno‐privilege properties of the CNS reduce or delay rejection of transplanted allo‐ and xeno‐islets. In addition, a plentiful nutrients and oxygen supply to the brain provide adequate insulin response to the increased glucose level resulting in rapid normoglycaemia in diabetic animals (Bloch et al, ; Tze and Tai, ).…”

Anti‐diabetic and neuroprotective effects of pancreatic islet transplantation into the central nervous system

“…Recently, we found that isolated syngeneic pancreatic islet transplanted in the cranial subarachnoid cavity of STZ‐diabetic Lewis rats resulted in long‐term normoglycemia and enabled the assembly of grafted islets directly onto the glomeruli of the olfactory bulb. The grafted islets expressed intact morphology, strong staining for three main pancreatic hormones (insulin, glucagon and somatostatin) and retained a typical rodent islet cell composition and architecture . Graft rejection from the brain was also addressed.…”

Comment on Gray et al. Insulin Regulates Brain Function, but How Does It Get There? Diabetes 2014;63:3992–3997

“…Recently, we suggested that pancreatic islets intracranially grafted into the rat subarachnoid space may serve as a promising tool for insulin delivery to the brain for treatment of cognitive dysfunctions (2,3). To test this hypothesis, islets were grafted into the subarachnoid space around the olfactory bulb and prefrontal cortex of rats displaying schizophrenia-like behavioral dysfunctions induced by exposure to dizocilpine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor.…”