Effect of hypovolemia on traumatic spinal cord injury

Sampaio, O de Cassia; Defino, Helton Luíz Aparecido; Guimarães, Elaine Aparecida Del Bel Belluz

doi:10.1038/sc.2016.26

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…The inclined plane test (IPT) is used to assess gross motor function in animal models with severe injury, such as SCI [ 25 , 26 ]. The mouse is placed on an inclined board to assess its ability to maintain position for at least 5 s without falling.…”

Section: Methodsmentioning

confidence: 99%

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

et al. 2016

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Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10–12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI.

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Section: Methodsmentioning

confidence: 99%

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

et al. 2016

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“…The IPT is used to assess gross motor function in animal models with severe injury, such as SCI . The mouse is placed on an inclined board to assess its ability to maintain position for at least 5 seconds without falling.…”

Section: Methodsmentioning

confidence: 99%

“…The IPT is used to assess gross motor function in animal models with severe injury, such as SCI. 43,44 The mouse is placed on an inclined board to assess its ability to maintain position for at least 5 seconds without falling. The board is raised in 5° increments during the process, and the maximum angle at which the mouse can maintain position is recorded.…”

Section: Inclined Plane Testmentioning

confidence: 99%

A novel translocator protein 18 kDa ligand, ZBD‐2, exerts neuroprotective effects against acute spinal cord injury

Cheng

Sun

Liu

et al. 2016

Clin Exp Pharma Physio

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Traumatic spinal cord injury (SCI) happens accidently and often leads to motor dysfunction due to a series of biochemical and pathological events and damage, either temporarily or permanently. Translocator protein 18 (TSPO) has been found to be involved in the synthesis of endogenous neurosteroids which have multiple effects on neurons, but the internal mechanisms are not clear. N-benzyl-N-ethyl-2-(7,8-oxo-2-phenyl-9H-purin-9-yl) acetamide (ZBD-2), a newly reported ligand of TSPO, shows some neuroprotective effect against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro. The present study aims to examine the role of ZBD-2 in SCI mice and elucidate the underlying molecular mechanisms. The SCI model was established by crushing spinal cord. ZBD-2 (10 mg/kg) significantly enhanced the hindlimb locomotor functions after SCI and decreased the tissue damage and conserved the white matter of the spinal cord. High-dose ZBD-2 alleviated the oxidative stress induced by SCI and regulated the imbalance between NR2B-containing NMDA and GABA receptors by increasing the levels of GAD67 in the spinal cord of SCI mice. Additionally, ZBD-2 (10 mg/kg) increased phosphorylated Akt (p-Akt) and decreased the ratio of Bax/Bcl-2. These results demonstrate that ZBD-2 performs neuroprotection against SCI through regulating the synaptic transmission and the PI3K/AKT signaling pathway.

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“…Primary injury indicates immediate physical damage to the spinal cord emanating from the contusion, concussion, compression, contraction, shear, and laceration of the neural tissue [ 2 ]. After some minutes following a primary injury, secondary injury is triggered, and it involves changes in the local ionic concentrations, loss of regulation of local and systemic blood pressure, reduced spinal cord blood flow, breakdown of the blood–brain barrier, penetration of serum proteins into the spinal cord, free radicals/lipid peroxidation production, inflammatory responses (alterations in cytokines and chemokines), apoptosis, excitotoxicity, calpain proteases, neurotransmitter aggregation, and imbalance of activated metalloproteinases [ 3 , 4 , 5 ]. These changes invariably lead to ischemia, edema, hypoxia, loss of myelin, necrosis, apoptosis of spinal cord tissue, glial cell proliferation, and the disconnection of living neurons, culminating in the formation of a microenvironment that is unfavorable for nerve regeneration [ 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Improved Locomotor Recovery in a Rat Model of Spinal Cord Injury by BioLuminescent-OptoGenetic (BL-OG) Stimulation with an Enhanced Luminopsin

Ikefuama

Kendziorski

Anderson

et al. 2022

IJMS

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Irrespective of the many strategies focused on dealing with spinal cord injury (SCI), there is still no way to restore motor function efficiently or an adequate regenerative therapy. One promising method that could potentially prove highly beneficial for rehabilitation in patients is to re-engage specific neuronal populations of the spinal cord following SCI. Targeted activation may maintain and strengthen existing neuronal connections and/or facilitate the reorganization and development of new connections. BioLuminescent-OptoGenetics (BL-OG) presents an avenue to non-invasively and specifically stimulate neurons; genetically targeted neurons express luminopsins (LMOs), light-emitting luciferases tethered to light-sensitive channelrhodopsins that are activated by adding the luciferase substrate coelenterazine (CTZ). This approach employs ion channels for current conduction while activating the channels through treatment with the small molecule CTZ, thus allowing non-invasive stimulation of all targeted neurons. We previously showed the efficacy of this approach for improving locomotor recovery following severe spinal cord contusion injury in rats expressing the excitatory luminopsin 3 (LMO3) under control of a pan-neuronal and motor-neuron-specific promoter with CTZ applied through a lateral ventricle cannula. The goal of the present study was to test a new generation of LMOs based on opsins with higher light sensitivity which will allow for peripheral delivery of the CTZ. In this construct, the slow-burn Gaussia luciferase variant (sbGLuc) is fused to the opsin CheRiff, creating LMO3.2. Taking advantage of the high light sensitivity of this opsin, we stimulated transduced lumbar neurons after thoracic SCI by intraperitoneal application of CTZ, allowing for a less invasive treatment. The efficacy of this non-invasive BioLuminescent-OptoGenetic approach was confirmed by improved locomotor function. This study demonstrates that peripheral delivery of the luciferin CTZ can be used to activate LMOs expressed in spinal cord neurons that employ an opsin with increased light sensitivity.

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Effect of hypovolemia on traumatic spinal cord injury

Cited by 5 publications

References 13 publications

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

A novel translocator protein 18 kDa ligand, ZBD‐2, exerts neuroprotective effects against acute spinal cord injury

Improved Locomotor Recovery in a Rat Model of Spinal Cord Injury by BioLuminescent-OptoGenetic (BL-OG) Stimulation with an Enhanced Luminopsin

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