The Affinity of Lipid-coated Microbubbles to Maturing Spinal Cord Injury Sites

The Affinity of Lipid-coated Microbubbles to Maturing Spinal Cord Injury Sites AbstractOBJECTIVEThis laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region.METHODSThe accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3'-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3'-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy.RESULTSThere was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury on postinjury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7.CONCLUSIONAffinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

The Affinity of Lipid-coated Microbubbles to Maturing Spinal Cord Injury Sites

The Affinity of Lipid-coated Microbubbles to Maturing Spinal Cord Injury Sites

EXPERIMENTAL STUDIES The Affinity of Lipid-coated Microbubbles to Maturing Spinal Cord Injury Sites Inam U. Kureshi, M .D ., Shih-Yieh Ho, Ph.D., Hilary C. Onyiuke, M .D., Andrew E. Wakefield, M .D., Ikram U. Kureshi, B.A., Joseph S. D'Arrigo, Ph.D., Richard H. Simon, M.D. Department of Surgery (InUK, S-YH, H C O , AEW , RHS), Division of Neurosurgery, University of Connecticut Health Center, and C A V -C O N , Inc. (JSD'A), Farmington, Connecticut; and Texas Tech University Health Science Center (IkUK), School of Medicine, Lubbock, Texas OBJECTIVE: This l a b o r a t o r y has d e m o n s t r a t e d t h a t l i p id - c o a t e d m i c r o b u b b l e s ( L C M s ) e f f e c t i v e l y a g g r e g a te a n d d eliver c h e m o t h e r a p e u t i c d ru g s in to r a t b r a in t u m o r cells a n d a n tig lio s is a g en ts in to m a t u r i n g r a t b r a in in ju r y sites. In this s tu d y , w e r e p o r t t h e a f f i n i t y o f ta il v e i n - i n j e c t e d L C M s to th e in j u r e d r a t s p in al c o r d b y a c o m p r e s s iv e lesion to th e u p p e r t h o r a c i c r e g io n . M E T H O D S : T h e a c c u m u la t io n o f L C M s in th e in ju re d spinal c o rd w as a n a ly z e d by la b e lin g it w i t h a lip id -s o lu b le fluorescent dye, 3 ,3 '- d io c t a d e c y lo x a c a r b o c y a n in e p e rc h lo ra te . Indices o f glial fib r illa r y a c id ic p ro te in w e r e m ea s u re d co nco m itantly w i t h 3 ,3 '- d io c t a d e c y lo x a c a r b o c y a n in e p e r c h lo r a te -la b e le d L C M s using c o n fo c a l m ic ro s c o p y . RESULTS: T h e r e w a s n o a g g r e g a t io n o f L C M s a c c u m u l a t e d 1 a n d 6 h o u rs a f t e r in ju r y ; h o w e v e r , w h e n g iv e n 2 , 4 , a n d 7 days a f t e r i n j u r y , L C M s s h o w e d a c l e a r a f f i n i t y f o r th e i n ju r e d r e g io n . L C M a g g r e g a tio n s h ifte d f r o m t h e c e n t r a l n ecro tic...
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Publisher
Congress of Neurological Surgeons
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199905000-00059
Publisher site
See Article on Publisher Site

Abstract

AbstractOBJECTIVEThis laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region.METHODSThe accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3'-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3'-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy.RESULTSThere was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury on postinjury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7.CONCLUSIONAffinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites.

Journal

NeurosurgeryOxford University Press

Published: May 1, 1999

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