EFFECT OF SPINAL-CORD INJURY ON THE PERMEABILITY OF THE BLOOD-BRAIN AND BLOOD SPINAL-CORD BARRIERS TO THE NEUROTROPIN PACAP

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been sh own to be a potent neurotropin. Because PACAP crosses the blood-brain barrier (BBB) by peptide transport system (PTS)-6, it can exert its ne urotropic effects even when given peripherally. Recent studies have sh own that the activity of BBB transporters of peptides and regulatory p roteins can be affected by pathophysiological events, including spinal cord injury. We, therefore, determined whether PTS-B is affected by s pinal cord injury, We found that radioactively iodinated PACAP was tak en up by brain and by all regions of the spinal cord. PTS-6 activity w as demonstrable in the brain and the cervical and thoracic regions of the spinal cord. Spinal cord transection had widespread and long-lasti ng effects throughout the CNS on PTS-6 activity, The most dramatic eff ect was an anatomically descending decrease of PTS-6 activity that beg an in the brain immediately after injury, Later, beginning on day 7 af ter injury, PTS-6 activity was increased throughout the CNS. These eff ects on PTS-6 were unrelated to the negligible disruption of barrier f unction 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.