Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

Area of Science:

• Neuroscience
• Endocrinology
• Pathology

Background:

• Diabetes mellitus (type 1 and type 2) is linked to numerous central nervous system (CNS) complications.
• These complications include stroke, vascular dementia, cognitive deficits, and neurochemical/electrophysiological/behavioral changes.
• Blood-brain barrier (BBB) damage is increasingly recognized as a key factor in diabetes-induced CNS disorders.

Purpose of the Study:

• To review current knowledge on how diabetes impacts BBB integrity and function.
• To examine the specific effects of hyperglycemia and hypoglycemia on brain microvasculature.
• To explore the role of the receptor for advanced glycation end products (RAGE) in diabetes-related CNS issues.

Main Methods:

• Review of existing literature and research findings on diabetes and the CNS.
• Analysis of studies investigating BBB transport functions, integrity, and oxidative stress in diabetic models.
• Examination of the relationship between hyperglycemia, cerebral ischemia, and secondary brain injury.

Main Results:

• Diabetes alters BBB transport functions, integrity (e.g., tight junction disruption), and induces oxidative stress in CNS microcapillaries.
• Upregulation and activation of RAGE may play a causal role in diabetes-dependent CNS disorders.
• Hyperglycemia is associated with the progression of cerebral ischemia and enhanced secondary brain injury.
• Controversial findings exist regarding diabetes's effects on the BBB due to challenges in in vivo studies.

Conclusions:

• Diabetes significantly impacts BBB integrity and function, contributing to various CNS complications.
• Both hyperglycemia and hypoglycemia play critical roles in these detrimental effects.
• Understanding these mechanisms is crucial for developing therapeutic strategies for diabetic neurological disorders.