Streaming Potential of White Matter and Gray Matter in Bovine Spinal Cord under Compressive Loading

After spinal cord injury (SCI), the inability of supraspinal neurons to regenerate or reform functional connections is likely due to proteins in the surrounding microenvironment restricting regeneration. EphAs are a family of receptor tyrosine kinases that are involved in axonal guidance during development. These receptors and their ligands, the Ephrins, act via repulsive mechanisms to guide growing axons towards their appropriate targets and allow for the correct developmental connections to be made. In the present study, we investigated whether EphA receptor expression changed after a thoracic contusion SCI. Our results indicate that several EphA molecules are upregulated after SCI. Using semiquantitative RT-PCR to investigate mRNA expression after SCI, we found that EphA3, A4, and A7 mRNAs were upregulated. EphA3, A4, A6, and A8 receptor immunoreactivity increased in the ventrolateral white matter (VWM) at the injury epicenter. EphA7 had the highest level of immunoreactivity in both control and injured rat spinal cord. EphA receptor expression in the white matter originated from glial cells as coexpression in both astrocytes and oligodendrocytes was observed. In contrast, gray matter expression was localized to neurons of the ventral gray matter (motor neurons) and dorsal horn. After SCI, specific EphA receptor subtypes are upregulated and these increases may create an environment that is unfavorable for neurite outgrowth and functional regeneration.

Download Full-text

Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/spi.2001.94.2.0257 ◽

2001 ◽

Vol 94 (2) ◽

pp. 257-264 ◽

Cited By ~ 8

Author(s):

Mercedes Zurita ◽

Jesús Vaquero ◽

Isabel Zurita

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Gray Matter ◽

Spinal Cord Tissue ◽

Injured Spinal Cord ◽

Content Type ◽

Cord Injury ◽

Positive Immunostaining ◽

Fine Print

Object. A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. Methods. The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. Conclusions. These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.

Download Full-text

Effects of Glycine Administration on Canine Experimental Spinal Spasticity and the Levels of Glycine, Glutamate, and Aspartate in the Lumbar Spinal Cord

Neurosurgery ◽

10.1227/00006123-197902000-00008 ◽

1979 ◽

Vol 4 (2) ◽

pp. 152-156 ◽

Cited By ~ 12

Author(s):

J. E. Smith ◽

P. V. Hall ◽

M. R. Galvin ◽

A. R. Jones ◽

R. L. Campbell

Keyword(s):

Spinal Cord ◽

White Matter ◽

Gray Matter ◽

Clinical Signs ◽

Spinal Cord Transection ◽

Lumbar Spinal Cord ◽

Central Gray Matter ◽

Central Gray ◽

Lumbar Spinal

Abstract Twelve female mongrel dogs were made paraplegic by midthoracic spinal cord transection. Beginning at 9 weeks posttransection, either glycine (50 mg/kg) or saline was injected intramuscularly each day and the signs of spinal spasticity were assessed clinically. After treating the dogs for 3 weeks, we removed the lumbar enlargement of each dog and microdissected it into gray and white areas which we assayed for glycine, glutamate, and aspartate content. Some of the clinical signs of spasticity improved in the animals injected with glycine compared to the saline-injected controls. The content of glycine was significantly elevated in the central gray matter and ventral medial white matter of the glycinetreated dogs. The levels of glutamate were also significantly elevated in the central, lateral ventral, and medial ventral gray matter and in the dorsal lateral and ventral medial white matter of the glycine-treated dogs. The possible role of these segmental putative neurotransmitters in spinal spasticity is discussed.

Download Full-text

Effect of aminophylline and isoproterenol on spinal cord blood flow after impact injury

Journal of Neurosurgery ◽

10.3171/jns.1980.53.3.0385 ◽

1980 ◽

Vol 53 (3) ◽

pp. 385-390 ◽

Cited By ~ 30

Author(s):

Diana Dow-Edwards ◽

Vincent DeCrescito ◽

John J. Tomasula ◽

Eugene S. Flamm

Keyword(s):

Spinal Cord ◽

Blood Flow ◽

White Matter ◽

Cord Blood ◽

Gray Matter ◽

Adenosine Monophosphate ◽

Spinal Cord Blood Flow ◽

Content Type ◽

Cord Injury ◽

Matter Flow

✓ A study of the effects of spinal cord injury upon spinal cord blood flow was carried out in cats. A 400 gm-cm impact produced an overall reduction in spinal cord blood flow of 24% in the white matter and 30% in the gray matter, as determined by 14C-antipyrine autoradiography. At the level of the injury, white-matter flow was 8.1 ml/100 gm/min, a reduction of 49%, and in the gray matter, 12.5 ml/100 gm/min, a reduction of 76%. Treatment with aminophylline and isoproterenol improved the overall blood flow in the spinal cord. At the level of the injury, white-matter flow after this treatment was no longer significantly different from control values. The gray-matter flow remained decreased to 26.2 ml/100 gm/min, a reduction of only 47%. It is proposed that aminophylline and isoproterenol may increase cyclic adenosine monophosphate (AMP) and prevent platelet aggregation along the endothelial surfaces of the microcirculation, and may thereby help to maintain improved perfusion of the injured spinal cord.

Download Full-text

Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) Model

10.1101/857946 ◽

2019 ◽

Author(s):

Niranjan Khadka ◽

Xijie Liu ◽

Hans Zander ◽

Jaiti Swami ◽

Evan Rogers ◽

...

Keyword(s):

Spinal Cord ◽

White Matter ◽

Open Source ◽

Electric Fields ◽

Epidural Space ◽

Gray Matter ◽

Spinal Cord Stimulation ◽

Clinical Trial Design ◽

Element Model ◽

Scs Model

AbstractObjectiveComputational current flow models of spinal cord stimulation (SCS) are widely used in device development, clinical trial design, and patient programming. Proprietary models of varied sophistication have been developed. An open-source model with state-of-the-art precision would serve as a standard for SCS simulation.ApproachWe developed a sophisticated SCS modeling platform, named Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) model. This platform consists of realistic and detailed spinal cord and ancillary tissues anatomy derived based on prior imaging and cadaveric studies. Represented tissues within the T9-T11 spine levels include vertebrae, intravertebral discs, epidural space, dura, CSF, white-matter, gray-matter, dorsal and ventral roots and rootlets, dorsal root ganglion, sympathetic chain, thoracic aorta, epidural space vasculature, white-matter vasculature, and thorax. As an exemplary, a bipolar SCS montage was simulated to illustrate the model workflow from the electric field calculated from a finite element model (FEM) to activation thresholds predicted for individual axons populating the spinal cord.Main ResultsCompared to prior models, RADO-SCS meets or exceeds detail for every tissue compartment. The resulting electric fields in white and gray-matter, and axon model activation thresholds are broadly consistent with prior stimulations.SignificanceThe RADO-SCS can be used to simulate any SCS approach with both unprecedented resolution (precision) and transparency (reproducibility). Freely available online, the RADO-SCS will be updated continuously with version control.

Download Full-text

An Attenuated Variant of the GDVII Strain of Theiler’s Virus Does Not Persist and Does Not Infect the White Matter of the Central Nervous System

Journal of Virology ◽

10.1128/jvi.73.1.801-804.1999 ◽

1999 ◽

Vol 73 (1) ◽

pp. 801-804 ◽

Cited By ~ 11

Author(s):

Nadine Jarousse ◽

Ekaterina G. Viktorova ◽

Evgeny V. Pilipenko ◽

Vadim I. Agol ◽

Michel Brahic

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

White Matter ◽

Gray Matter ◽

Noncoding Region ◽

Theiler's Virus ◽

Recombinant Viruses ◽

Central Nervous Systems ◽

The Central Nervous System

ABSTRACT The DA strain of Theiler’s virus causes a persistent and demyelinating infection of the white matter of spinal cord, whereas the GDVII strain causes a fatal gray-matter encephalomyelitis. Studies with recombinant viruses showed that this difference in phenotype is controlled mainly by the capsid. However, conflicting results regarding the existence of determinants of persistence in the capsid of the GDVII strain have been published. Here we show that a GDVII virus whose neurovirulence has been attenuated by an insertion in the 5′ noncoding region does not persist in the central nervous systems of mice. Furthermore, this virus infects the gray matter efficiently, but not the white matter. These results confirm the absence of determinants of persistence in the GDVII capsid. They suggest that the DA capsid controls persistence by allowing the virus to infect cells in the white matter of the spinal cord.

Download Full-text

Properties of convective delivery in spinal cord gray matter: laboratory investigation and computational simulations

Journal of Neurosurgery Spine ◽

10.3171/2015.5.spine141148 ◽

2016 ◽

Vol 24 (2) ◽

pp. 359-366 ◽

Cited By ~ 3

Author(s):

Toshiki Endo ◽

Yushi Fujii ◽

Shin-ichiro Sugiyama ◽

Rong Zhang ◽

Shogo Ogita ◽

...

Keyword(s):

Spinal Cord ◽

White Matter ◽

Gray Matter ◽

Computational Models ◽

Computational Simulation ◽

Regional Distribution ◽

Volume Of Distribution ◽

Blue Dye ◽

White Matter Tract ◽

Computational Simulations

OBJECT Convection-enhanced delivery (CED) is a method for distributing small and large molecules locally into the interstitial space of the spinal cord. Delivering these molecules to the spinal cord is otherwise difficult due to the blood-spinal cord barrier. Previous research has proven the efficacy of CED for delivering molecules over long distances along the white matter tracts in the spinal cord. Conversely, the characteristics of CED for delivering molecules to the gray matter of the spinal cord remain unknown. The purpose of this study was to reveal regional distribution of macromolecules in the gray and white matter of the spinal cord with special attention to the differences between the gray and white matter. METHODS Sixteen rats (F344) underwent Evans blue dye CED to either the white matter (dorsal column, 8 rats) or the gray matter (ventral horn, 8 rats) of the spinal cord. The rates and total volumes of infusion were 0.2 μl/min and 2.0 μl, respectively. The infused volume of distribution was visualized and quantified histologically. Computational models of the rat spinal cord were also obtained to perform CED simulations in the white and gray matter. RESULTS The ratio of the volume of distribution to the volume of infusion in the gray matter of the spinal cord was 3.60 ± 0.69, which was comparable to that of the white matter (3.05 ± 0.88). When molecules were injected into the white matter, drugs remained in the white matter tract and rarely infused into the adjacent gray matter. Conversely, when drugs were injected into the gray matter, they infiltrated laterally into the white matter tract and traveled longitudinally and preferably along the white matter. In the infusion center, the areas were larger in the gray matter CED than in the white matter (Mann-Whitney U-test, p < 0.01). In computational simulations, the aforementioned characteristics of CED to the gray and white matter were reaffirmed. CONCLUSIONS In the spinal cord, the gray and white matter have distinct characteristics of drug distribution by CED. These differences between the gray and white matter should be taken into account when considering drug delivery to the spinal cord. Computational simulation is a useful tool for predicting drug distributions in the normal spinal cord.

Download Full-text

Dorsal and ventral horn atrophy is associated with clinical outcome after spinal cord injury

Neurology ◽

10.1212/wnl.0000000000005361 ◽

2018 ◽

Vol 90 (17) ◽

pp. e1510-e1522 ◽

Cited By ~ 11

Author(s):

Eveline Huber ◽

Gergely David ◽

Alan J. Thompson ◽

Nikolaus Weiskopf ◽

Siawoosh Mohammadi ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Clinical Outcome ◽

Gray Matter ◽

Ventral Horn ◽

Tissue Specific ◽

Weighted Sequence ◽

Cord Injury ◽

Lesion Severity

ObjectiveTo investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury.MethodsA 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome.ResultsNeurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence.ConclusionOur results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.

Download Full-text