Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers.
The possibility that serotonin can take part in the initiation of the increased microvascular permeability occurring in a spinal cord trauma was investigated in a rat model with 131I-sodium and lanthanum as tracers. We influenced the serotonin content in the tissue pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA), before the production of the injury and compared the results with injured, untreated controls. A small incision was made in the dorsal horn of the lower thoracic cord. It caused a progressive extravasation of 131I-sodium in the damaged segment, measured after 1, 2 and 5 h. Rostral and caudal segments also showed a significant but lower accumulation of 131I-sodium. Lanthanum added to the fixative was used as an ionic tracer detectable by electron microscopy. The endothelial cells of microvessels removed from the perifocal region after 5 h showed a marked increase in the number of lanthanum-filled vesicles. Many endothelial cells had a diffuse penetration of the tracer into the cytoplasm and the basement membrane. However, the tight junctions usually remained closed to lanthanum. Pretreatment with p-CPA markedly reduced the extravasation of 131I-sodium measured at 5 h in the traumatized cord. At the cellular level, the endothelial vesicles filled with lanthanum approached the condition of uninjured animals. The diffuse infiltration of lanthanum into endothelial cells and its spread into the basement membrane of the vascular wall were usually absent. Our results indicate that serotonin plays a role in the initiation of the increased microvascular permeability which occurs in spinal cord injuries.
Olsson
Y
Y
Institute of Pathology, University Hospital, Uppsala, Sweden.
Sharma
H S
HS
Pettersson
C A
CA
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D010134:Fenclonine / Q000494:pharmacology*; D007811:Lanthanum / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*
D012979:Sodium Radioisotopes; D012701:Serotonin; D007811:Lanthanum; D010134:Fenclonine