Header

UZH-Logo

Maintenance Infos

Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier


Mäe, Maarja Andaloussi; Li, Tian; Bertuzzi, Giacomo; Raschperger, Elisabeth; Vanlandewijck, Michael; He, Liqun; Nahar, Khayrun; Dalheim, Annika; Hofmann, Jennifer J; Laviña, Bàrbara; Keller, Annika; Betsholtz, Christer; Genové, Guillem (2018). Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier. Scientific Reports, 8:17462.

Abstract

Diabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer's disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocin-induced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature. Here we used a genetic mouse model of hyperglycemia (Ins2AKITA) to address whether prolonged systemic hyperglycemia induces BBB dysfunction and leakage. We applied a variety of methodologies to carefully evaluate BBB function and cellular integrity in vivo, including the quantification and visualization of specific tracers and evaluation of transcriptional and morphological changes in the BBB and its supporting cellular components. These experiments did neither reveal altered BBB permeability nor morphological changes of the brain vasculature in hyperglycemic mice. We conclude that prolonged hyperglycemia does not lead to BBB dysfunction, and thus the cognitive impairment observed in diabetes may have other causes.

Abstract

Diabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer's disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocin-induced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature. Here we used a genetic mouse model of hyperglycemia (Ins2AKITA) to address whether prolonged systemic hyperglycemia induces BBB dysfunction and leakage. We applied a variety of methodologies to carefully evaluate BBB function and cellular integrity in vivo, including the quantification and visualization of specific tracers and evaluation of transcriptional and morphological changes in the BBB and its supporting cellular components. These experiments did neither reveal altered BBB permeability nor morphological changes of the brain vasculature in hyperglycemic mice. We conclude that prolonged hyperglycemia does not lead to BBB dysfunction, and thus the cognitive impairment observed in diabetes may have other causes.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

3 downloads since deposited on 08 Jan 2019
3 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurosurgery
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:1 December 2018
Deposited On:08 Jan 2019 15:42
Last Modified:13 Jan 2019 13:04
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-018-35576-0
PubMed ID:30498224
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P2_150735
  • : Project TitleArithmetic and Geometry of algebraic points on varieties

Download

Download PDF  'Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier'.
Preview
Content: Published Version
Filetype: PDF
Size: 4MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)