Blood–Spinal Cord Barrier Pericyte Reductions Contribute to Increased Capillary Permeability

• Published in: Journal of cerebral blood flow and metabolism Vol. 32; no. 10; pp. 1841 - 1852
• Main Authors: Winkler, Ethan A, Sengillo, Jesse D, Bell, Robert D, Wang, Joseph, Zlokovic, Berislav V
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.10.2012; Nature Publishing Group; Sage Publications Ltd
• Subjects: Animals; Biological and medical sciences; Brain; Brain - blood supply; Capillary Permeability; Cell Count; Cerebral blood flow; Data processing; Down-Regulation; Endocrinopathies; fibrin; Fluorescent indicators; Male; Medical sciences; Membrane permeability; Mice; Motor neurons; Motor Neurons - cytology; Motor Neurons - pathology; Mutation; Neurology; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Occludin - genetics; pericytes; Pericytes - cytology; Pericytes - pathology; Rapid Communication; Serum proteins; Spinal cord; Spinal Cord - blood supply; Spinal Cord - cytology; Spinal Cord - pathology; Thorax; Thrombin; Thyroid. Thyroid axis (diseases); Tight Junction Proteins - genetics; Tight junctions; Tight Junctions - metabolism; Tight Junctions - pathology; Vascular diseases and vascular malformations of the nervous system; Zonula occludens-1 protein; endothelium; vascular biology; blood–brain barrier; capillaries; pericytes; Pericyte; Spinal cord; Nervous system diseases; Permeability; Blood brain barrier; Cerebral disorder; Endothelium; blood―brain barrier; Central nervous system disease; Cerebrovascular disease
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2012.113

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 (PdgfrβF7/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.