TY - JOUR
T1 - A quantitative spatial analysis of the blood-spinal cord barrier I. Permeability changes after experimental spinal contusion injury
AU - Popovich, Phillip G.
AU - Horner, Philip J.
AU - Mullin, Bradford B.
AU - Stokes, Bradford T.
N1 - Funding Information:
The authors thank Dr. Joe Fenstermacher for his assistance in establishing the AIB technique in our laboratory and for his guidance during the preparation of the manuscript. Thank you also to Drs. Caroline Whitacre and Dana McTigue for their critical review of the manuscript. We also thank Ms. Ping Wei, Zhen Guan, and Yi-Fei Chen for their invaluable technical assistance and Patricia Walters for her constant support with animal care and injuries. This study was supported by NINDS training Grant T32 NS07291-05 (P.G.P.), NS 10165-21, and NS 33696 (B.T.S.), and the American Paralysis Association.
PY - 1996/12
Y1 - 1996/12
N2 - Blood-spinal cord barrier (BSB) permeability was measured using quantitative autoradiography following contusion injury to the rat spinal cord. Permeability was assessed by calculating blood-to-tissue transfer constants (K(i) values) for the vascular tracer [14C]-α-aminoisobutyric acid (AIB) in injured (3, 7, 14, and 28 days postinjury), laminectomy control, and uninjured control animals. Permeability was quantitated using four separate imaging techniques in gray and white matter throughout the rostro-caudal extents of the forming lesion. Away from the epicenter, gray matter permeability was further differentiated within 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 both 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 (~6-9 ml/kg/min). By 7 days, K(i) values were quantitatively smaller (~4-5 ml/kg/min) in all regions compared with 3-day tissues. Despite further attenuation of AIB uptake in the gray matter at 14 and 28 days postinjury, circumferential white matter tracts showed a secondary increase in permeability compared to 7-day tissue. Permeability in the white matter at 14-28 days postinjury (~5-6 ml/kg/min) was comparable to that at 3 days postinjury (6-7 ml/kg/min). Measurements of the axial distribution of AIB permeability indicate increased BSB permeability over several segments rostral and caudal to the lesion epicenter (~3 cm in both directions). Secondary elevations of AIB transfer in the spinal white matter between 14 and 28 days were colocalized with zones of immunohistochemically defined microglial clusters. The known plasticity of this cell type in response to changes in the extracellular microenvironment suggests that the spinal white matter at later survival times (14-28 days postinjury) is an area of dynamic vascular and/or axonal reconstruction. The implications of increased permeability to both tissue injury and neural regeneration are discussed.
AB - Blood-spinal cord barrier (BSB) permeability was measured using quantitative autoradiography following contusion injury to the rat spinal cord. Permeability was assessed by calculating blood-to-tissue transfer constants (K(i) values) for the vascular tracer [14C]-α-aminoisobutyric acid (AIB) in injured (3, 7, 14, and 28 days postinjury), laminectomy control, and uninjured control animals. Permeability was quantitated using four separate imaging techniques in gray and white matter throughout the rostro-caudal extents of the forming lesion. Away from the epicenter, gray matter permeability was further differentiated within 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 both 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 (~6-9 ml/kg/min). By 7 days, K(i) values were quantitatively smaller (~4-5 ml/kg/min) in all regions compared with 3-day tissues. Despite further attenuation of AIB uptake in the gray matter at 14 and 28 days postinjury, circumferential white matter tracts showed a secondary increase in permeability compared to 7-day tissue. Permeability in the white matter at 14-28 days postinjury (~5-6 ml/kg/min) was comparable to that at 3 days postinjury (6-7 ml/kg/min). Measurements of the axial distribution of AIB permeability indicate increased BSB permeability over several segments rostral and caudal to the lesion epicenter (~3 cm in both directions). Secondary elevations of AIB transfer in the spinal white matter between 14 and 28 days were colocalized with zones of immunohistochemically defined microglial clusters. The known plasticity of this cell type in response to changes in the extracellular microenvironment suggests that the spinal white matter at later survival times (14-28 days postinjury) is an area of dynamic vascular and/or axonal reconstruction. The implications of increased permeability to both tissue injury and neural regeneration are discussed.
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U2 - 10.1006/exnr.1996.0196
DO - 10.1006/exnr.1996.0196
M3 - Article
C2 - 8934558
AN - SCOPUS:0030560684
SN - 0014-4886
VL - 142
SP - 258
EP - 275
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -