Role of the blood-spinal cord barrier in posttraumatic syringomyelia

2009 ◽  
Vol 11 (6) ◽  
pp. 696-704 ◽  
Author(s):  
Sarah J. Hemley ◽  
B. Biotech ◽  
Jian Tu ◽  
Marcus A. Stoodley
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Vascular Permeability ◽  
Neurological Deficits ◽  
Time Points ◽  
Functional Integrity ◽  
Cord Injury ◽  
Posttraumatic Syringomyelia ◽  
Blood Spinal Cord Barrier

Object Posttraumatic syringomyelia produces a significant burden of pain and neurological deficits in patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. A possible explanation for syrinx formation is fluid leakage from the microcirculation in the presence of a compromised blood-spinal cord barrier (BSCB). The aim of this study was to investigate the structural and functional integrity of the BSCB in a model of posttraumatic syringomyelia. Methods The excitotoxic amino acid and arachnoiditis model of syringomyelia was used in 27 Sprague-Dawley rats. Structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen (EBA), and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidase. Animals were studied after 3 days, or at 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection control animals for comparison at each time point. Results Syrinxes formed in 16 of the 17 animals injected with excitotoxic amino acid. Loss of structural and functional integrity of the BSCB in syrinx animals was noted at all time points. Disruption of the BSCB was most dramatic in tissue adjacent to the syrinx, and in the central and dorsal gray matter. Changes in EBA expression generally corresponded with altered vascular permeability, although in the acute stages, widespread vascular permeability occurred without a corresponding decrease in EBA expression. At the later time points (3–12 weeks) EBA expression was often absent, although no vascular leakage was observed. Conclusions This study demonstrated a prolonged structural and functional disruption of the BSCB in this model of posttraumatic syringomyelia. Loss of functional integrity of the BSCB, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst, to produce posttraumatic syringomyelia.

scholarly journals Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Chongan Huang ◽  
Weiqi Zhang ◽  
FeiFan Chu ◽  
Hao Qian ◽  
Yining Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Neurological Deficits ◽  
Critical Event ◽  
Neuroprotective Effects ◽  
Patchouli Alcohol ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier

Spinal cord injury (SCI) is a destructive and complex disorder of the central nervous system (CNS) for which there is no clinical treatment. Blood-spinal cord barrier (BSCB) rupture is a critical event in SCI that aggravates nerve injury. Therefore, maintaining the integrity of the BSCB may be a potential method to treat SCI. Here, we showed that patchouli alcohol (PA) exerts protective effects against SCI. We discovered that PA significantly prevented hyperpermeability of the BSCB by reducing the loss of tight junctions (TJs) and endothelial cells. PA also suppressed endoplasmic reticulum stress and apoptosis in vitro. Furthermore, in a rat model of SCI, PA effectively improved neurological deficits. Overall, these results prove that PA exerts neuroprotective effects by maintaining BSCB integrity and thus be a promising candidate for SCI treatment.

scholarly journals Beneficial “Pharmaceutical Pleiotropy” of Gabapentinoids in Spinal Cord Injury: A Case for Refining Standard-of-Care

2020 ◽  
Vol 34 (8) ◽  
pp. 686-689
Author(s):  
Jacquelyn J. Cragg ◽  
Catherine R. Jutzeler ◽  
Lukas Grassner ◽  
Matt Ramer ◽  
Frank Bradke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Standard Of Care ◽  
Neurological Deficits ◽  
Standards Of Care ◽  
Complementary Approach ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Blood Spinal Cord Barrier

Spinal cord injury results in devastating neurological deficits accompanied by lifelong disability and significant economic burden. While the development of novel compounds or cell-based interventions for spinal cord injury is unquestionably worthwhile, a complementary approach examines current standards of care and the degree to which these can be optimized to benefit long-term neurological function. Numerous classes of drugs, already in use in the acute phase of spinal cord injury, are intriguing because they (1) readily cross the blood-spinal cord barrier to modulate activity in the central nervous system and (2) are administered during a window of time in which neuroprotection, and even some repair, are feasible. Here, we review a rare case of convergent lines of evidence from both preclinical and human studies to support the early administration of a class of drug (ie, gabapentinoids) to both foster motor recovery and reduce the severity of neuropathic pain.

Rehabilitation of the canine patient following spinal cord injury: a practical guide

2021 ◽  
Vol 26 (1) ◽  
pp. 1-6
Author(s):  
Cheryl Corral
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Neurological Deficits ◽  
Practical Guide ◽  
Cord Injury ◽  
Physical Therapies

This article forms part of a series exploring the rehabilitation of the canine shoulder, elbow, back, hip and stifle following injury or disease. Discussed here are different rehabilitation techniques used to address neurological deficits, pain and weakness following spinal injury, including physical therapies, electrotherapies and acupuncture.

scholarly journals Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christian Blume ◽  
M. F. Geiger ◽  
M. Müller ◽  
H. Clusmann ◽  
V. Mainz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurological Status ◽  
Consecutive Series ◽  
Inflammatory Reactions ◽  
Immune Mediated ◽  
Elisa Testing ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Angiopoietin 2

AbstractEndogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

scholarly journals Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

2020 ◽  
Vol 9 (4) ◽  
pp. 1221 ◽  
Author(s):  
Jacek M. Kwiecien ◽  
Liqiang Zhang ◽  
Jordan R. Yaron ◽  
Lauren N. Schutz ◽  
Christian J. Kwiecien-Delaney ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Low Dose ◽  
Dorsal Column ◽  
Neurological Deficits ◽  
Sustained Delivery ◽  
Post Surgery ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

A Sensitive Fluorometric Method for Measurement of Vascular Permeability in Spinal Cord Injury

1991 ◽  
Vol 8 (2) ◽  
pp. 149-156 ◽  
Author(s):  
ZHI-XIANG QU ◽  
JIAN XU ◽  
PHANOR L. PEROT ◽  
EDWARD L. HOGAN
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vascular Permeability ◽  
Fluorometric Method ◽  
Cord Injury

scholarly journals Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1697-1713 ◽  
Author(s):  
Xingxing Wang ◽  
Tianna Zhou ◽  
George D Maynard ◽  
Pramod S Terse ◽  
William B Cafferty ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Recovery Of Function ◽  
Neurological Deficits ◽  
Vehicle Group ◽  
Post Injury ◽  
Nogo Receptor ◽  
Human Dose ◽  
Cord Injury ◽  
Human Primate

Abstract After CNS trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal Nogo receptor 1 (NgR1). A soluble decoy (NgR1-Fc, AXER-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical rodent models of spinal cord injury. However, the safety and efficacy of this reagent in non-human primate spinal cord injury and its toxicological profile have not been described. Here, we provide evidence that chronic intrathecal and intravenous administration of NgR1-Fc to cynomolgus monkey and to rat are without evident toxicity at doses of 20 mg and greater every other day (≥2.0 mg/kg/day), and far greater than the projected human dose. Adult female African green monkeys underwent right C5/6 lateral hemisection with evidence of persistent disuse of the right forelimb during feeding and right hindlimb during locomotion. At 1 month post-injury, the animals were randomized to treatment with vehicle (n = 6) or 0.10–0.17 mg/kg/day of NgR1-Fc (n = 8) delivered via intrathecal lumbar catheter and osmotic minipump for 4 months. One animal was removed from the study because of surgical complications of the catheter, but no treatment-related adverse events were noted in either group. Animal behaviour was evaluated at 6–7 months post-injury, i.e. 1–2 months after treatment cessation. The use of the impaired forelimb during spontaneous feeding and the impaired hindlimb during locomotion were both significantly greater in the treatment group. Tissue collected at 7–12 months post-injury showed no significant differences in lesion size, fibrotic scar, gliosis or neuroinflammation between groups. Serotoninergic raphespinal fibres below the lesion showed no deficit, with equal density on the lesioned and intact side below the level of the injury in both groups. Corticospinal axons traced from biotin-dextran-amine injections in the left motor cortex were equally labelled across groups and reduced caudal to the injury. The NgR1-Fc group tissue exhibited a significant 2–3-fold increased corticospinal axon density in the cervical cord below the level of the injury relative to the vehicle group. The data show that NgR1-Fc does not have preclinical toxicological issues in healthy animals or safety concerns in spinal cord injury animals. Thus, it presents as a potential therapeutic for spinal cord injury with evidence for behavioural improvement and growth of injured pathways in non-human primate spinal cord injury.

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