Pericytes impair capillary blood flow and motor function after chronic spinal cord injury


Blood vessels in the central nervous system (CNS) are controlled by neuronal activity. For example, widespread vessel constriction (vessel tone) is induced by brainstem neurons that release the monoamines serotonin and noradrenaline, and local vessel dilation is induced by glutamatergic neuron activity. Here we examined how vessel tone adapts to the loss of neuron-derived monoamines after spinal cord injury (SCI) in rats. We find that, months after the imposition of SCI, the spinal cord below the site of injury is in a chronic state of hypoxia owing to paradoxical excess activity of monoamine receptors (5-HT1) on pericytes, despite the absence of monoamines. This monoamine-receptor activity causes pericytes to locally constrict capillaries, which reduces blood flow to ischemic levels. Receptor activation in the absence of monoamines results from the production of trace amines (such as tryptamine) by pericytes that ectopically express the enzyme aromatic L-amino acid decarboxylase (AADC), which synthesizes trace amines directly from dietary amino acids (such as tryptophan). Inhibition of monoamine receptors or of AADC, or even an increase in inhaled oxygen, produces substantial relief from hypoxia and improves motoneuron and locomotor function after SCI.

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Figure 1: Trace amines constrict capillaries at pericytes after SCI.
Figure 2: AADC, trace amines and 5-HT1B receptors are coexpressed in pericytes after SCI.
Figure 3: Poor blood flow and hypoxia after chronic SCI.
Figure 4: Treatments that dilate vessels and improve oxygenation after SCI lead to increased motor activity.
Figure 5: Thoracic contusion or staggered-hemisection injury induces chronic hypoxia that impairs locomotion.


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We thank F. Geddes and Y. Ma for technical assistance. This research was supported by the Canadian Institutes of Health Research (MOP 14697; D.J.B.) and the US National Institutes of Health (NIH, R01NS47567; D.J.B. and K.F.).

Author information

Y.L. performed all in vitro rat experiments and in vivo pO2 measurements, contributed to all other rat studies and co-wrote the paper. R.V. and K.F. contributed to the rat in vivo locomotor experiments. I.R.W., K.F., R.V., L.S. and A.M.L.-O. contributed to immunolabeling experiments. I.R.W., L.S. and M.V.B. contributed to blood flow measurements. L.S. performed all sacral SCI surgeries. M.J.S., S.B. and K.K.F. contributed to analysis and editing. A.F.D.N. and S.D. performed mRNA-seq analysis. D.J.B. performed in vitro and in vivo rat experiments, directly supervised all the experiments and co-wrote the paper. K.F. and D.J.B. shared senior authorship.

Correspondence to David J Bennett.

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Li, Y., Lucas-Osma, A., Black, S. et al. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury. Nat Med 23, 733–741 (2017).

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