Dataset Information

Dietary therapy to promote neuroprotection in chronic spinal cord injury.

ABSTRACT: The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission.An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period.At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane.Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.

SUBMITTER: Holly LT

PROVIDER: S-EPMC3951955 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dietary therapy to promote neuroprotection in chronic spinal cord injury.

Holly Langston T LT Blaskiewicz Donald D Wu Aiguo A Feng Cameron C Ying Zhe Z Gomez-Pinilla Fernando F

Journal of neurosurgery. Spine 20120626 2

<h4>Object</h4>The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission.<h4>Methods</h4>An animal model of CSM was created using a nonresorbable expandable polymer pl ...[more]

PMID: 22735048

Similar Datasets

Project description:BackgroundSpinal cord injury (SCI) usually causes a devastating lifelong disability for patients. After a traumatic lesion, disruption of the blood-spinal cord barrier induces the infiltration of macrophages into the lesion site and the activation of resident glial cells, which release cytokines and chemokines. These events result in a persistent inflammation, which has both detrimental and beneficial effects, but eventually limits functional recovery and contributes to the appearance of neuropathic pain. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that regulate the expression of inflammatory genes by interacting with acetylated lysine residues. While BET inhibitors are a promising therapeutic strategy for cancer, little is known about their implication after SCI. Thus, the current study was aimed to investigate the anti-inflammatory role of BET inhibitors in this pathologic condition.MethodsWe evaluated the effectiveness of the BET inhibitor JQ1 to modify macrophage reactivity in vitro and to modulate inflammation in a SCI mice model. We analyzed the effects of BET inhibition in pro-inflammatory and anti-inflammatory cytokine production in vitro and in vivo. We determined the effectiveness of BET inhibition in tissue sparing, inflammation, neuronal protection, and behavioral outcome after SCI.ResultsWe have found that the BET inhibitor JQ1 reduced the levels of pro-inflammatory mediators and increased the expression of anti-inflammatory cytokines. A prolonged treatment with JQ1 also decreased reactivity of microglia/macrophages, enhanced neuroprotection and functional recovery, and acutely reduced neuropathic pain after SCI.ConclusionsBET protein inhibition is an effective treatment to regulate cytokine production and promote neuroprotection after SCI. These novel results demonstrate for the first time that targeting BET proteins is an encouraging approach for SCI repair and a potential strategy to treat other inflammatory pathologies.

Project description:With emerging applications of spinal cord electrical stimulation in restoring autonomic and motor function after spinal cord injury, understanding the neuroanatomical substrates of the human spinal cord after spinal cord injury using neuroimaging techniques can play a critical role in optimizing the outcomes of these stimulation-based interventions. In this study, we have introduced a neuroimaging acquisition and analysis protocol of the spinal cord in order to identify: (i) spinal cord levels at the lumbosacral enlargement using nerve root tracing; (ii) variability in the neuroanatomical characteristics of the spinal cord among individuals; (iii) location of the epidural stimulation paddle electrode and contacts with respect to the spinal cord levels at lumbosacral enlargement; and (iv) the links between the anatomical levels of stimulation and the corresponding neurophysiological motor responses. Twelve individuals with chronic, motor complete spinal cord injury implanted with a spinal cord epidural stimulator were included in the study (age: 34 ± 10.9 years, sex: 10 males, 2 females, time since injury: 8.2 ± 9.9 years, American Spinal Injury Association Impairment Scale: 6 A, 6 B). High-resolution MRI scans of the spinal cord were recorded pre-implant. An analysis of neuroanatomical substrates indicates that the length of the spinal column and spinal cord, location of the conus tip and the relationship between the spinal cord levels and vertebral levels, particularly at the lumbosacral enlargement, are variable across individuals. There is no statistically significant correlation between the length of the spinal column and the length of the spinal cord. The percentage of volumetric coverage of the lumbosacral spinal cord by the epidural stimulation paddle electrode ranges from 33.4 to 90.4% across participants. The location of the spinal cord levels with respect to the electrode contacts varies across individuals and impacts the recruitment patterns of neurophysiological responses. Finally, MRI-based spinal cord modelling can be used as a guide for the prediction and preplanning of optimum epidural stimulation paddle placement prior to the implant surgery to ensure maximizing functional outcomes. These findings highlight the crucial role that the neuroanatomical characteristics of the spinal cord specific to each individual play in achieving maximum functional benefits with spinal cord electrical stimulation.

Dataset Information

Dietary therapy to promote neuroprotection in chronic spinal cord injury.

Publications

Dietary therapy to promote neuroprotection in chronic spinal cord injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets