Impact of vasculature damage on the outcome of spinal cord injury: a novel collagenase-induced model may give new insights into the mechanisms involved

Losey, Patrick; Anthony, Daniel C.

doi:10.4103/1673-5374.143422

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…However, to date, the translation of these promising outcomes from the lab to the bedside has been without success (Martirosyan et al, 2011 ; Varma et al, 2013 ). The type of SCI most frequently induced is dependent on the mechanical impact of the injury which can then be categorized into: compression, contusion, distraction, dislocation, transection, collagenase and ischemia-reperfusion (interruption of blood flow) injury (IRI; Choo et al, 2007 , 2008 , 2009 ; Akhtar et al, 2008 ; Rummery et al, 2010 ; Cheriyan et al, 2014 ; Losey and Anthony, 2014 ; Kato et al, 2015 ; Figure 1 ). Each of these models bears many advantages, but is not without some limitations (Akhtar et al, 2008 ; Choo et al, 2008 ; Rummery et al, 2010 ; Cheriyan et al, 2014 ; Losey and Anthony, 2014 ).…”

Section: Animal Models For Scimentioning

confidence: 99%

“…However, the microvascular system (centrifugal) delivers blood to a large portion of gray matter (mostly neurons) and inner half of the white matter (mostly myelinated tracts). Furthermore, the pial microarterial bed, in conjunction with outlets from branches of posterior arteries, provides blood to the posterior white matter and dorsal horns (Losey and Anthony, 2014 ). Interestingly, the gray matter is highly vascularized compared to white matter, which has a lower metabolic rate due to low arterial density (Martirosyan et al, 2011 ).…”

Section: Inflammatory Effects On Circulationmentioning

confidence: 99%

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Inflammogenesis of Secondary Spinal Cord Injury

Anwar

Shehabi

Eid

2016

Front. Cell. Neurosci.

355

258

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Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine.

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Section: Animal Models For Scimentioning

confidence: 99%

Section: Inflammatory Effects On Circulationmentioning

confidence: 99%

Inflammogenesis of Secondary Spinal Cord Injury

Anwar

Shehabi

Eid

2016

Front. Cell. Neurosci.

355

258

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“…As such, SCI can generally be divided into different clinical phases: Acute SCI—with destruction of the blood‐brain barrier, alterations to the microvasculature of the grey matter and induction of petechial haemorrhages, which has also been linked with the formation of oedema, thrombin production and erythrocyte lysis. Vascular changes and haemorrhages fulfil a crucial role in the initial pathological events leading to neuronal cell death and axonal damage (Gerzanich et al, ; Griffiths, Burns, & Crawford, ; Losey & Anthony, ; Losey, Young, Krimholtz, Bordet, & Anthony, ; Yu & Fehlings, ). The presence of inflammatory cells can also be observed, especially that of neutrophils, which have been detected as soon as 3 min after a contusion injury and that are related to the extent of injury (Griffiths et al, ; Taoka et al, ; Yu & Fehlings, ).…”

Section: Introductionmentioning

confidence: 99%

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Gómez

Sanchez

Portela-Lomba

et al. 2018

Glia

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The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.

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“…In the study of SCI, several species of experimental animals, for example, pigs (Jones et al, ; Lee et al, ; Šulla et al, ), dogs (Fujimaki et al, ; Bozynski et al, ; Sarmento et al, ), cats (Tsitsopoulos et al, ; Gu et al, ; Murphy et al, ), rabbits (Fang et al, ; Leonard et al, ; Mechírová et al, ), guinea pigs (Ouyang et al, ; Galle et al, ; Sun et al, ), rats (Chung et al, ; Losey and Anthony, ; Soubeyrand et al, ), and mice (Abematsu et al, ; Awad et al, ; Gaviria et al, 2012) are used.…”

mentioning

confidence: 99%

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review

Mazensky

Flešárová

Šulla

2017

The Anatomical Record

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Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc.

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Impact of vasculature damage on the outcome of spinal cord injury: a novel collagenase-induced model may give new insights into the mechanisms involved

Cited by 15 publications

References 22 publications

Inflammogenesis of Secondary Spinal Cord Injury

Inflammogenesis of Secondary Spinal Cord Injury

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review

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