Spinal Cord Compression Injury in Guinea Pigs: Structural Changes of Endothelium and Its Perivascular Cell Associations after Blood–Brain Barrier Breakdown and Repair

Jaeger, Christine; Blight, Andrew R.

doi:10.1006/exnr.1996.6405

Cited by 63 publications

(44 citation statements)

References 69 publications

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“…The current literature, mostly based on in vitro studies, indicates that BSCB permeability to large plasma proteins in the injured SC is resolved within 14 to 17 days after a traumatic insult (3,23). On the other hand, Popovich et al (4) reported an increased permeability to smaller molecules (i.e., 14 C-a-aminoisobutyric acid (AIB)) up to 1 month postinjury both at and away from the center of a contusion-type SCI.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in BSCB permeability can be followed experimentally using intravascularly administered tracers (such as plasma proteins, radiolabeled proteins, and small-molecular-weight molecules) that can cross the compromised barrier (3,4). Although these tracer-based techniques provide valuable information about the status of BSCB, they are either fully invasive, necessitating histological analysis of tissue, or less invasive but still requiring intravenous injection of radio-tracers with subsequent blood sampling along with imaging, as in the case of autoradiography.…”

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confidence: 99%

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Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

Bilgen¹,

Abbe²,

Narayana³

2001

Magnetic Resonance in Med

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The progression of experimental spinal cord injury (SCI) was followed with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and neurobehavioral studies on postinjury days 0, 2, 4, 7, 10, 14, 17, 21, 28, 35, and 42. Gadopentate dimeglumine (Gd) was administered IV and postcontrast, T 1 -weighted, axial images were acquired repetitively for up to 60 min. Images were analyzed to determine the spatial and temporal evolution of the intensity enhancement. A statistical decision mechanism was developed to objectively detect the enhancement. Strong and rapid enhancement was observed at the epicenter of injury, indicating a significant compromise in blood spinal cord barrier. The enhanced regions in each slice were combined to estimate the area and volume of the lesion. On the day of injury, around 85% of the total cord area at the epicenter showed enhancement within the first 15 min of Gd administration. At the same time, the enhanced volumes attained nearly 40% of the total cord volume and extended axially over 8 mm along the cord. The blood-spinal cord barrier (BSCB) maintains a highly regulated homeostatic environment in the spinal cord (SC) tissue. This regulatory function is sustained by various structures, including the capillary endothelial tight junctions. Under normal physiological conditions, BSCB protects the cord tissue by exhibiting selective permeability to the constituents of intravascular fluid (1,2). A traumatic insult to SC disrupts the structural and biochemical integrity of BSCB. The altered tight junctional patency allows vesicular transport of toxic substances from blood plasma to interstitial spaces. This makes the SC tissue environment unfavorable for neuronal survival, and inhibits tissue repair processes and neurologic recovery. By following the changes in BSCB after injury, important information may be gained about the regions of initial SC tissue damage and a time window for effective drug delivery across the barrier. Assessing BSCB in the late phases of the injury may help evaluate the progression of spinal cord injury (SCI) as well as the efficacy of potential therapeutic interventions.Changes in BSCB permeability can be followed experimentally using intravascularly administered tracers (such as plasma proteins, radiolabeled proteins, and small-molecular-weight molecules) that can cross the compromised barrier (3,4). Although these tracer-based techniques provide valuable information about the status of BSCB, they are either fully invasive, necessitating histological analysis of tissue, or less invasive but still requiring intravenous injection of radio-tracers with subsequent blood sampling along with imaging, as in the case of autoradiography. Moreover, active transport mechanisms involved in some of these tracers may introduce a bias in quantifying the BSCB permeability (4).As an alternative to the above techniques, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with the exogenous paramagnetic contrast agent gadopentetate-dimeglumine (Gd, for short)...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

Bilgen¹,

Abbe²,

Narayana³

2001

Magnetic Resonance in Med

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“…6,7 Moreover, secondary injuries and chronic functional deficits after SCI are associated with alterations of the microvasculature, 8 including increased BBB permeability, 9 modified vascular morphology, [10][11][12] and BM duplication. 13,14 Further, the giant protein AHNAK (700 kDa), expressed in an intact central nervous system (CNS) only by endothelial cells and pericytes, and specifically associated with tight junctions (TJ) of blood vessels belonging to the BBB, 15 is strongly expressed within the lesion site, both in blood vessels and in cells forming at later stages post-injury the inner border of cystic cavities, in front of the astrocytic scar. 12 Interestingly, after SCI, CSPG expression remains detectable at the interface of reactive astrocytes and AHNAK-positive cells even at long term.…”

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confidence: 99%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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Upregulation of extracellular chondroitin sulfate proteoglycans (CSPG) is a primary cause for the failure of axons to regenerate after spinal cord injury (SCI), and the beneficial effect of their degradation by chondroitinase ABC (ChABC) is widely documented. Little is known, however, about the effect of ChABC treatment on astrogliosis and revascularization, two important factors influencing axon regrowth. This was investigated in the present study. Immediately after a spinal cord hemisection at thoracic level 8-9, we injected ChABC intrathecally at the sacral level, repeated three times until 10 days post-injury. Our results show an effective cleavage of CSPG glycosaminoglycan chains and stimulation of axonal remodeling within the injury site, accompanied by an extended period of astrocyte remodeling (up to 4 weeks). Interestingly, ChABC treatment favored an orientation of astrocytic processes directed toward the injury, in close association with axons at the lesion entry zone, suggesting a correlation between axon and astrocyte remodeling. Further, during the first weeks post-injury, ChABC treatment affected the morphology of laminin-positive blood vessel basement membranes and vessel-independent laminin deposits: hypertrophied blood vessels with detached or duplicated basement membrane were more numerous than in lesioned untreated animals. In contrast, at later time points, laminin expression increased and became more directly associated with newly formed blood vessels, the size of which tended to be closer to that found in intact tissue. Our data reinforce the idea that ChABC injection in combination with other synergistic treatments is a promising therapeutic strategy for SCI repair.

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“…As a result blood circulation within the lesioned area is re-established. Vascular repair coincides with a permanent increase in the number of capillary pro®les in the lesion area and with long-term changes of the blood±brain barrier including reduced astrocyte±en-dothelial cell association, expansion of perivascular space and prominent ECM deposits (Jaeger and Blight, 1997).…”

Section: Responses Of Nonneuronal Cellsmentioning

confidence: 86%

Experimental strategies to promote axonal regeneration after traumatic central nervous system injury

Stichel

Müller

1998

Progress in Neurobiology

123

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AbstractÐA damage or pathological process that destroys the continuity of axons in the mature central nervous system (CNS) has devastating consequences and produces lasting functional de®cits. One of the major challenges in this ®eld is to stimulate the regrowth of severed axons and reconstruction of pathways. Recent progress in molecular and cell biology has resulted in an explosion of knowledge on factors in the adult CNS being nonsupportive or even actively inhibitory to axonal regrowth. The new ®ndings have a strong impact on the development of new therapeutic concepts directed to stimulate axonal regeneration. They give rise to cautious optimism, showing that under some circumstances repair of a CNS lesion is possible. In this review the authors summarize the current knowledge on the factors and mechanisms involved in regeneration failure and provide an overview of the current therapeutic approaches that may enable eective CNS regeneration in the future. #

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Spinal Cord Compression Injury in Guinea Pigs: Structural Changes of Endothelium and Its Perivascular Cell Associations after Blood–Brain Barrier Breakdown and Repair

Cited by 63 publications

References 69 publications

Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Experimental strategies to promote axonal regeneration after traumatic central nervous system injury

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