Effect of spinal cord injury on the permeability of the blood-brain and blood-spinal cord barriers to the neurotropin PACAP

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be a potent neurotropin. Because PACAP crosses the blood-brain barrier (BBB) by peptide transport system (PTS)-6, it can exert its neurotropic effects even when given peripherally. Recent studies have shown that the activity of BBB transporters of peptides and regulatory proteins can be affected by pathophysiological events, including spinal cord injury. We, therefore, determined whether PTS-6 is affected by spinal cord injury. We found that radioactively iodinated PACAP was taken up by brain and by all regions of the spinal cord. PTS-6 activity was demonstrable in the brain and the cervical and thoracic regions of the spinal cord. Spinal cord transection had widespread and long-lasting effects throughout the CNS on PTS-6 activity. The most dramatic effect was an anatomically descending decrease of PTS-6 activity that began in the brain immediately after injury. Later, beginning on day 7 after injury, PTS-6 activity was increased throughout the CNS. These effects on PTS-6 were unrelated to the negligible disruption of barrier function by the injury. We conclude that spinal cord injury results in responses that are regionally and temporally unique to PTS-6 and could affect the delivery of blood-borne PACAP to the CNS.