A QUANTITATIVE SPATIAL-ANALYSIS OF THE BLOOD SPINAL-CORD BARRIER .1. PERMEABILITY CHANGES AFTER EXPERIMENTAL SPINAL CONTUSION INJURY

Blood-spinal cord barrier (BSB) permeability was measured using quanti tative autoradiography following contusion injury to the rat spinal co rd. Permeability was assessed by calculating blood-to-tissue transfer constants (K-i values) for the vascular tracer [C-14]-alpha-aminoisobu tyric acid (AIB) in injured (3, 7, 14, and 28 days postinjury), lamine ctomy control, and uninjured control animals. Permeability was quantit ated using four separate imaging techniques in gray and white matter t hroughout the rostro-caudal extents of the forming lesion. Away from t he epicenter, gray matter permeability was further differentiated with in discrete spinal lamina using computerized templates. Regardless of the type of analysis used, increased AIB permeability (K-i values) was noted at all survival times in all tissue regions with respect to bot h uninjured and laminectomy control groups. The data indicate a large increase in individual K-i values throughout the dorsoventral axis of the spinal cord at 3 days postinjury (similar to 6-9 ml/kg/min). By 7 days, K-i values were quantitatively smaller (similar to 4-5 ml/kg/min ) in all regions compared with 3-day tissues. Despite further attenuat ion of AIB uptake in the gray matter at 14 and 28 days postinjury, cir cumferential white matter tracts showed a secondary increase in permea bility compared to 7-day tissue. Permeability in the white matter at 1 4-28 days postinjury (similar to 5-6 ml/kg/min) was comparable to that at 3 days postinjury (6-7 ml/kg/min). Measurements of the axial distr ibution of AIB permeability indicate increased BSB permeability over s everal segments rostral and caudal to the lesion epicenter (similar to 3 cm in both directions). Secondary elevations of AIB transfer in the spinal white matter between 14 and 28 days were colocalized with zone s of immunohistochemically defined microglial clusters. The known plas ticity of this cell type in response to changes in the extracellular m icroenvironment suggests that the spinal white matter at later surviva l times (14-28 days postinjury) is an area of dynamic vascular and/or axonal reconstruction. The implications of increased permeability to b oth tissue injury and neural regeneration are discussed. 1996 Academic Press, Inc.