Dietary Omega-3 Deficiency from Gestation Increases Spinal Cord Vulnerability to Traumatic Brain Injury-Induced Damage

Ying, Zhe; Feng, Cameron; Agrawal, Rahul; Zhuang, Yizhou; Gómez‐Pinilla, Fernando

doi:10.1371/journal.pone.0052998

Cited by 16 publications

(14 citation statements)

References 23 publications

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“…To our knowledge, this is the only research that has demonstrated remote lesions in the spine following mTBI. This may further help explain the impaired synaptic plasticity and reduced plasma membrane homeostasis in the lumbar spine as recently reported 6 . This has significant implications for future research and understand the distal muscular atrophy and complex regional pain symptoms often seen with patients following TBI.…”

Section: Discussionsupporting

confidence: 59%

“…Studies investigating how inflammation and maladaptive plasticity compromise spinal cord integrity at sites distant to the initial TBI are almost nonexistent. Zing et al, recently reported that TBI reduced levels of critical “molecular systems important for synaptic plasticity (BDNF, TrkB, and CREB) and plasma membrane homeostasis (4-HNE, iPLA2, syntaxin-3) in the lumbar spinal cord” 6 . Chen et al, showed that there are more distant neurodegenerative changes at sites uninvolved by the initial TBI, including increased neuronal degeneration and inflammation involving the ipsilateral hippocampus and thalamus between sham and injured groups who had received a mild controlled cortical contusion (CCI) 7 .…”

Section: Introductionmentioning

confidence: 99%

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Magnetic Resonance Imaging Tracking of Distal Inflammatory Changes following Mild Traumatic Brain Injury (mTBI) in rats

Gillham

Figueroa

Bartnik

2016

Preprint

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Sensorimotor disturbances continue to represent one of the most debilitating and widely reported complications in patients suffering mild traumatic brain injuries (mTBI). Loss of peripheral neuronal function at sites distal and disconnected to the central nervous control central centers is well documented. Distal muscular atrophy, complex regional pain symptoms, and poor wound healing are just a few of the many complications with often more severe secondary complications such decubitus ulcers and osteomyelitis seen at sites in the body distal to the center of injury. MRI has been widely established as a diagnostic and therapeutic planning tool in patients and animal models with neuronal disease. However, studies investigating the neural correlates of spinal cord changes after TBI are lacking. Here, we used T2 MR imaging to determine the effects of mTBI on the morphology and inflammatory changes of the spinal cord. We hypothesize that rats receiving mTBI utilizing a controlled cortical impact (CCI) contusion will demonstrate T2 signal changes at distal locomotor centers in the spine. Experimental mTBI and sham groups of Sprague-Dawley rats were used (n = 2 sham and 4 experimental). A mild CCI was applied to the right brain cortex. Rats were sacrificed at 60 days post injury and spinal cords harvested for ex vivo MRI T2 analysis. Focal areas/lesions of increased T2 hyperintensity were noted in mTBI injured rats (n = 4).Experimental group of rats also demonstrated secondary spinal cord locomotor and sensation adverse effects clinically. MR imaging showed volumetric reductions and T2 signal changes in the cervical, thoracic, and lumbar segments of the spinal cord at 8 weeks' post-injury. T2 intensity values were elevated in all experimental groups in comparison to the sham group within the distal cord, suggesting that remote CCI causes secondary spinal cord inflammation and neurodegeneration at distant sites.These findings also further support the idea that the most peripheral nerves and spinal cord will be most negatively affected by a TBI. While our research is in its preliminary stages, our results further confirm that mTBI has more far reaching effects than previously understood. T2 MRI is an effective tool to assess the extent of spinal cord injury related to antecedent TBI. Introduction:Mild traumatic brain injury (TBI) is well known to lead to substantial socioeconomic cost and serious secondary consequences 1-3 . Although mTBI is often associated with good prognosis, it remains one of the leading causes of disability and death among children and young adults. TBI represents a huge economic burden to our society, with estimated total annual cost of 76.5 billion 4,5 . Sensory and motor disturbances are among the most debilitating consequences of mTBI, resulting in longer hospital stays and delayed recovery during rehabilitation.It is unclear how a cortical concussive injury can affect distant spinal cord centers. Studies investigating how inflammation and maladaptive plasticity compromise spinalcord integrity a...

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Imaging Tracking of Distal Inflammatory Changes following Mild Traumatic Brain Injury (mTBI) in rats

Gillham

Figueroa

Bartnik

2016

Preprint

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“…Fluidity of plasma membrane plays important roles for cellular functions such as signal transduction, cell recognition, membrane order and the funtion of membrane receptors; flexibility of plasma membrane could increase membrane stability, which can adapt to challenge of different conditions (Lafourcade et al, ; Yamashima, ). The ratio of n‐3/n‐6 has a positive correlation with membrane fluidity and flexibility, which can be involved in antioxidative effects and upregulate the expression of antioxidant enzyme genes in NSCs Fat‐1 to enhance the capacity of scavenging ROS (Hasadsri et al, ; Lee et al, ; Ying, Feng, Agrawal, Zhuang, & Gomez‐Pinilla, ).…”

Section: Discussionmentioning

confidence: 99%

mfat‐1 transgene protects cultured adult neural stem cells against cobalt chloride‐mediated hypoxic injury by activating Nrf2/ARE pathways

Yang

Fang

et al. 2017

J of Neuroscience Research

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Ischemic stroke is a devastating neurological disorder and one of the leading causes of death and serious disability in adults. Adult neural stem cell (NSC) replacement therapy is a promising treatment for both structural and functional neurological recovery. However, for the treatment to work, adult NSCs must be protected against hypoxic-ischemic damage in the ischemic penumbra. In the present study, we aimed to investigate the neuroprotective effects of the mfat-1 transgene on cobalt chloride (CoCl 2 )-induced hypoxic-ischemic injury in cultured adult NSCs as well as its underlying mechanisms. The results show that in the CoCl 2 -induced hypoxic-ischemic injury model, the mfat-1 transgene enhanced the viability of adult NSCs and suppressed CoCl 2 -mediated apoptosis of adult NSCs. Additionally, the mfat-1 transgene promoted the proliferation of NSCs as shown by increased bromodeoxyuridine labeling of adult NSCs. This process was related to the reduction of reactive oxygen species. Quantitative real-time polymerase chain reaction and Western blot analysis revealed a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes (HO-1, NQO-1, GCLC). Taken together, our findings show that the mfat-1 transgene restored the CoCl 2 -inhibited viability and proliferation of NSCs by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signal pathway to inhibit oxidative stress injury.

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“…Our work is consistent with several other studies where practice has improved performance on cognitive tasks, such as executive functioning and memory in military personnel (Bogdanova and Verfaellie, 2012). Additionally, both diet and exercise has been proven to be an effective remediation technique following TBI (Griesbach et al, 2009; Wu et al, 2011; Ying et al, 2012; Tyagi et al, 2013). Increased exercise in rodents within 2 days after injury improved cognitive deficits associated with object recognition memory (Chen et al, 2012) while an exercise regimen 3 months after injury improved working memory (Piao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

Sebastian¹,

Diallo²,

Ling³

et al. 2013

Front. Behav. Neurosci.

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Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

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Dietary Omega-3 Deficiency from Gestation Increases Spinal Cord Vulnerability to Traumatic Brain Injury-Induced Damage

Cited by 16 publications

References 23 publications

Magnetic Resonance Imaging Tracking of Distal Inflammatory Changes following Mild Traumatic Brain Injury (mTBI) in rats

Magnetic Resonance Imaging Tracking of Distal Inflammatory Changes following Mild Traumatic Brain Injury (mTBI) in rats

mfat‐1 transgene protects cultured adult neural stem cells against cobalt chloride‐mediated hypoxic injury by activating Nrf2/ARE pathways

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

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