MRI Metrics of Cerebral Endothelial Cell–Derived Exosomes for the Treatment of Cognitive Dysfunction Induced in Aging Rats Subjected to Type 2 Diabetes

Abstract

Ongoing neurovascular dysfunction contributes to type 2 diabetes mellitus (T2DM)-induced cognitive deficits. However, it is not known whether early post onset of T2DM interventions may reduce evolving neurovascular dysfunction and thereby lead to diminution of T2DM-induced cognitive deficits. Using multiple MRI metrics, we evaluated neurovascular changes in T2DM rats treated with exosomes derived from cerebral endothelial cells (CECExos). Two months after induction of T2DM in middleaged male rats by administration of streptozotocin nicotinamide, rats were randomly treated with CEC-Exos twice weekly or saline for 4 consecutive weeks (n 5 10/ group). MRI measurements were performed at the end of the treatment, which included cerebral blood flow (CBF), contrast-enhanced T1-weighted imaging, and relaxation time constants T1 and T2. MRI analysis showed that compared with controls, the CEC-Exo–treated T2DM rats exhibited significant elevation of T2 andCBFinwhitematter and significant augmentation of T1 and reduction of blood-brain barrier permeability in gray matter. In the hippocampus, CEC-Exo treatment significantly increased T1 and CBF. Furthermore, CEC-Exo treatment significantly reduced T2DM-induced cognitive deficits measured by the Morris water maze and odor recognition tests. Collectively, our corresponding MRI data demonstrate that treatment of T2DM rats with CEC-Exos robustly reduced neurovascular dysfunction in gray and white matter and the hippocampus.