Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Oct 14:1623:81-96.
doi: 10.1016/j.brainres.2015.02.045. Epub 2015 Mar 3.

Cellular connections, microenvironment and brain angiogenesis in diabetes: Lost communication signals in the post-stroke period

Adviye Ergul  1 , John Paul Valenzuela  2 , Abdelrahman Y Fouda  3 , Susan C Fagan  4
Affiliations
Review

Cellular connections, microenvironment and brain angiogenesis in diabetes: Lost communication signals in the post-stroke period

Adviye Ergul et al. Brain Res. .

Abstract

Diabetes not only increases the risk but also worsens the motor and cognitive recovery after stroke, which is the leading cause of disability worldwide. Repair after stroke requires coordinated communication among various cell types in the central nervous system as well as circulating cells. Vascular restoration is critical for the enhancement of neurogenesis and neuroplasticity. Given that vascular disease is a major component of all complications associated with diabetes including stroke, this review will focus on cellular communications that are important for vascular restoration in the context of diabetes. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

Keywords: Angiogenesis; Diabetes; Stroke; Vascular restoration.

PubMed Disclaimer

Figures

Figure 1
Figure 1. A schematic representation of the bidirectional interactions between various CNS and peripheral cell types that contribute to neurovascular repair after stroke
Diabetes impedes vascular restoration and functional recovery.
Figure 2
Figure 2. Possible mechanisms contributing to weakened pericyte-endothelial cell interactions in diabetes
A. At the initiation of angiogenesis, pericytes migrate away from endothelial cells and secrete proangiogenic growth factors like VEGF-A. Pericytes are later recruited in response to PDGF-β secreted by endothelial cells and through the activation of PDGF-R β, they proliferate and enhance the interaction with endothelial cells. Pericytes contribute to the termination of angiogenesis and stabilization of newly formed vessels through barriergenesis. Activation of TGF-β and Ang-1, stimulates expression of N-cadherin, integrins and gap junctions, especially connexin 43 (CX43). As vessel stabilization occurs, pericytes, along with astrocytes, secrete matrix proteins. B. In diabetes, pericyte recruitment, attachment and maturation are impaired. Increased phosphorylated pPDGFR-β, decreased PDGFR-β expression and or altereations in Ang-1 and Ang-2 signaling may contribute to loss of communication between these two cell types.
Figure 3
Figure 3. Diabetes reduces pericytes in the brain
Brain capillaries were isolated from control and diabetic Goto-Kakizaki rats 6–7 weeks after the onset of diabetes. Samples were allowed to adhere to cover slips and stained with nuclear stain DAPI. To determine the number of pericytes (PC), round nuclei were counted versus endothelial cells (EC) that have elongated nuclei.
Figure 4
Figure 4. Effect of diabetes on systemic cells’ functions after stroke
Bone marrow endothelial progenitor cells (EPC) produce angiogenic mediators and are incorporated in the newly formed vessels at the ischemic border zone after stroke. Diabetes reduces EPC count and angiogenic response. Diabetes increase neutrophil recruitment, activation and adhesion in the diabetic brain after stroke leading to increased inflammation. Diabetics have elevated levels of platelet-derived microparticles (PMP) putting them at risk of increased coagulation after ischemic stroke.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abaci A, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation. 1999;99:2239–42. - PubMed
    1. Abdelsaid M, et al. Metformin Treatment in Post-stroke Period Prevents Nitrative Stress and Restores Angiogenic Signaling in the Brain in Diabetes. Diabetes. 2014 Epub ahead of print. - PMC - PubMed
    1. Al-Gayyar MM, et al. Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity. Br J Pharmacol. 2011;164:170–80. - PMC - PubMed
    1. Alhusban A, et al. AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator. J Pharmacol Exp Ther. 2013;344:348–59. - PMC - PubMed
    1. Arai K, Lo EH. An oligovascular niche: cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J Neurosci. 2009;29:4351–5. - PMC - PubMed

Publication types