Blood–Spinal Cord Barrier Pericyte Reductions Contribute to Increased Capillary Permeability
Open accessAbstract
The blood–spinal cord barrier (BSCB) regulates molecular exchange between blood and spinal cord. Pericytes are presumed to be important cellular constituents of the BSCB. However, the regional abundance and vascular functions of spinal cord pericytes have yet to be determined. Utilizing wild-type mice, we show that spinal cord pericyte capillary coverage and number compared with the brain regions are reduced most prominently in the anterior horn. Regional pericyte variations are highly correlated with: (1) increased capillary permeability to 350 Da, 40,000 Da, and 150,000 Da, but not 2,000,000 Da fluorescent vascular tracers in cervical, thoracic, and lumbar regions and (2) diminished endothelial zonula occludens-1 (ZO-1) and occludin tight junction protein expression. Pericyte-deficient mutations ( Pdgfrβ F7/F7 mice) resulted in additional pericyte reductions in spinal cord capillaries leading to overt BSCB disruption to serum proteins, accumulation in motor neurons of cyotoxic thrombin and fibrin and motor neuron loss. Barrier disruption in perciyte-deficient mice coincided with further reductions in ZO-1 and occludin. These data suggest that pericytes contribute to proper function of the BSCB at the capillary level. Regional reductions in spinal cord pericytes may provide a cellular basis for heightened spinal cord barrier capillary permeability and motor neuron loss.
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In the case of Pdgfrß deficiency, blood-brain barrier breakdown and vascular phenotype precede neuronal degeneration and loss.
“In the case of Pdgfrß deficiency, BBB breakdown and vascular phenotype precede neuronal degeneration and loss (59, 319, 650), whereas pericyte-deficient Pdgfb ret/ret mice develop deep brain calcification at a later age resembling IBGC (309).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [650]
The Results report spinal cord barrier leakage and vascular abnormalities in PdgfrβF7/F7 mice, and motor-neuron loss in 13-month-old mice. The Animals section identifies the younger, 4- to 6-month-old mice used in the study. This supports a sequence involving the blood–spinal cord barrier, but the paper does not establish the claimed sequence for the blood–brain barrier and brain neuronal degeneration. (LLM, conf=0.87)
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- Authors
- Winkler, E. A., Sengillo, J. D., Bell, R. D., Wang, J., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- University of Rochester Medicine (US)
- Department of Physiology and Biophysics, University of Southern California, Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Los Angeles, California, USA
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2012-08-01
- Volume
- 32
- Issue
- 10
- Pages
- 1841-1852
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3463878
- OpenAlex
- W2052874642
- Cited by
- 226
- References
- 5
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 18 · 2020: 13 · 2019: 13 · 2018: 20 · 2017: 20 · 2016: 11 · 2015: 18 · 2014: 12 · 2013: 9 · 2012: 2
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG039452, AG039452, RF1AG039452)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- blood-spinal cord barrier, pericytes, capillary permeability, tight junctions, zonula occludens-1, occludin, ventral horn, motor neuron degeneration, thrombin, fibrin deposition, spinal cord vasculature
- MeSH terms
- Animals, Brain, Capillary Permeability, Cell Count, Male, Motor Neurons, Spinal Cord, Down-Regulation, Tight Junctions, Pericytes, Mice, Tight Junction Proteins, Occludin
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