Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia

So, tested in rats. IT IS YOUR DOCTORS AND HOSPITAL RESPONSIBILITY TO ENSURE HUMAN TESTING IS DONE. DOING NOTHING IS TOTAL FUCKING INCOMPETENCY. 

Oops, I'm not playing by the polite rules of Dale Carnegie,  'How to Win Friends and Influence People'. 

Politeness will never solve anything in stroke. Yes, I'm a bomb thrower and proud of it. Someday a stroke 'leader' will ream me out for making them look bad by being truthful , I look forward to that day. 

The latest here:

Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia

Su Jing Chan

,

Elga Esposito

,

Kazuhide Hayakawa

,

Emiri Mandaville

,

Raymond A.A. Smith

,

Shuzhen Guo

,

Wanting Niu

,

Peter Tsun-Hong Wong

,

Simon M. Cool

,

Eng H. Lo

,

Victor Nurcombe

Originally published10 Aug 2020https://doi.org/10.1161/STROKEAHA.119.025304Stroke. ;0

Abstract

Background and Purpose:

Although VEGF₁₆₅ (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF₁₆₅-binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function.

Methods:

Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed.

Results:

HS7 significantly enhanced VEGF₁₆₅-mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity.

Conclusions:

A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF₁₆₅ activity during the post-ischemic recovery phase of stroke.

Footnotes

For Sources of Funding and Disclosures, see page XXX

The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.119.025304.

Correspondence to: Victor Nurcombe, PhD, Glycotherapeutics Group (VNSC), Institute of Medical Biology (IMB), 8A Biomedical Grove, No. 06-06 Immunos, Singapore 138648, Email victor.nurcombe@imb.a-star.edu.sg or Eng Lo PhD, Massachusetts General Hospital, Neuroprotection Research Lab, Bldg 149, Room 2401, 149 13th St, Charlestown, MA 02129, Email lo@helix.mgh.harvard.edu