Depression-like behavior corresponds with cardiac changes in a rodent model of spinal cord injury

Brakel, Kiralyn; Aceves, Alejandro R.; Aceves, Miriam; Hierholzer, Ashton; Nguyen, Quynh‐Nhu

doi:10.1016/j.expneurol.2019.112969

Cited by 14 publications

(14 citation statements)

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“…Unfortunately, people living with SCI are much more likely to commit suicide with reports in England showing a 5-fold increase in per capita suicide rates (Savic et al, 2018). Furthermore, 28% of rats with T12 contusion SCI suffered from depression (Brakel et al, 2019) which was associated with increased serum levels of interleukin (IL)-6 and IL-1α before and IL-6 and tumor necrosis factor (TNF)-α after injury (Brakel et al, 2021). These findings imply predisposition to depression even before injury occurs if systemic increases in inflammation induces depression (Lee and Giuliani, 2019).…”

Section: Connection Between Sci Neurological Diseases and Hippocampal Neurogenesismentioning

confidence: 99%

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Sefiani

Geoffroy

2021

Front. Neurosci.

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Currently there are approximately 291,000 people suffering from a spinal cord injury (SCI) in the United States. SCI is associated with traumatic changes in mobility and neuralgia, as well as many other long-term chronic health complications, including metabolic disorders, diabetes mellitus, non-alcoholic steatohepatitis, osteoporosis, and elevated inflammatory markers. Due to medical advances, patients with SCI survive much longer than previously. This increase in life expectancy exposes them to novel neurological complications such as memory loss, cognitive decline, depression, and Alzheimer’s disease. In fact, these usually age-associated disorders are more prevalent in people living with SCI. A common factor of these disorders is the reduction in hippocampal neurogenesis. Inflammation, which is elevated after SCI, plays a major role in modulating hippocampal neurogenesis. While there is no clear consensus on the mechanism of the decline in hippocampal neurogenesis and cognition after SCI, we will examine in this review how SCI-induced inflammation could modulate hippocampal neurogenesis and provoke age-associated neurological disorders. Thereafter, we will discuss possible therapeutic options which may mitigate the influence of SCI associated complications on hippocampal neurogenesis.

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Section: Connection Between Sci Neurological Diseases and Hippocampal Neurogenesismentioning

confidence: 99%

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Sefiani

Geoffroy

2021

Front. Neurosci.

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“…However, depression-like behavior is also observed in animal models of SCI, in the absence of the socioeconomic challenges and changes in functional independence that may affect the clinical population. Approximately one-third of rats with SCI develop depression-like behavior, a percentage concomitant with the clinical population ( Brakel et al., 2019 ; Luedtke et al., 2014 ; Maldonado-Bouchard et al., 2016 ; Wu et al., 2014b ). Importantly, these rats do not exhibit depression-like behavior prior to injury ( Brakel et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Inflammation increases the development of depression behaviors in male rats after spinal cord injury

Brakel

Aceves

Garza

et al. 2021

Brain, Behavior, & Immunity - Health

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Following spinal cord injury, 18–26% of patients are diagnosed with depressive disorders, compared to 8–12% in the general population. As increased inflammation strongly correlates with depression in both animal and human studies, we hypothesized that the immune activation inherent to SCI could increase depression-like behavior. Thus, we proposed that reducing immune activation with minocycline, a microglial inhibitor, would decrease depression-like behavior following injury. Male Sprague-Dawley rats were given minocycline in their drinking water for 14 days following a moderate, mid-thoracic (T12) spinal contusion. An array of depression-like behaviors (social activity, sucrose preference, forced swim, open field activity) were examined prior to injury as well as on days 9–10, 19–20, and 29–30 post-injury. Peripheral cytokine levels were analyzed in serum collected prior to injury and 10 days post-injury. Hierarchical cluster analysis divided subjects into two groups based on behavior: depressed and not-depressed. Depressed subjects displayed lower levels of open field activity and social interaction relative to their not-depressed counterparts. Depressed subjects also showed significantly greater expression of pro-inflammatory cytokines both before and after injury and displayed lower levels of hippocampal neurogenesis than not-depressed subjects. Intriguingly, subjects who later showed depressive behaviors had higher baseline levels of the pro-inflammatory cytokine IL-6, which persisted throughout the duration of the experiment. Minocycline, however, did not affect serum cytokine levels and did not block the development of depression; equal numbers of minocycline versus vehicle-treated subjects appeared in both phenotypic groups. Despite this, these data overall suggest that molecular correlates of inflammation prior to injury could predict the development of depression after a physical stressor.

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“…Although these data were derived from control animals from a series of experiments, the surgery was carried out by the same investigators who had trained in the same laboratory and the experiments followed sequentially during a period from 2017 to 2019. Kruskal-Wallis testing did not detect difference in day 21 scores (H = 3.39; P = 0.50) between the animal groups created for the original experiments [including data published in (15)(16)(17)]. There was also considerable variability in recovery between individuals (Figure 2).…”

Section: Resultsmentioning

confidence: 96%

“…In this study we aimed to quantify the variability associated with a standardized spinal cord injury and BBB scoring applied over a 21-day follow-up period. The subjects for analysis were rats that were controls in previously published experiments (15)(16)(17), or will be included in future publications, and had undergone a moderate T12 spinal cord contusion but had not received systemic or intraspinal medications, nor spinal implants. Open-field scoring was carried out by investigators trained and experienced in the technique and blinded to treatment allocation.…”

Section: Methodsmentioning

confidence: 99%

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Variability in Open-Field Locomotor Scoring Following Force-Defined Spinal Cord Injury in Rats: Quantification and Implications

et al. 2020

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Spinal cord injury research in experimental animals aims to define mechanisms of tissue damage and identify interventions that can be translated into effective clinical therapies. Highly reliable models of injury and outcome measurement are essential to achieve these aims and avoid problems with reproducibility. Functional scoring is a critical component of outcome assessment and is currently commonly focused on open field locomotion (the “BBB score”). Here we analyze variability of observed locomotor outcome after a highly regulated spinal cord contusion in a large group of rats that had not received any therapeutic intervention. Our data indicate that, despite tight regulation of the injury severity, there is considerable variability in open-field score of individual rats at 21 days after injury, when the group as a whole reaches a functional plateau. The bootstrapped reference interval (that defines boundaries that contain 95% scores in the population without regard for data distributional character) for the score at 21 days was calculated to range from 2.3 to 15.9 on the 22-point scale. Further analysis indicated that the mean day 21 score of random groups of 10 individuals drawn by bootstrap sampling from the whole study population varies between 9.5 and 13.5. Wide variability between individuals implies that detection of small magnitude group-level treatment effects will likely be unreliable, especially if using small experimental group sizes. To minimize this problem in intervention studies, consideration should be given to assessing treatment effects by comparing proportions of animals in comparator groups that attain pre-specified criterion scores.

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Depression-like behavior corresponds with cardiac changes in a rodent model of spinal cord injury

Cited by 14 publications

References 70 publications

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Inflammation increases the development of depression behaviors in male rats after spinal cord injury

Variability in Open-Field Locomotor Scoring Following Force-Defined Spinal Cord Injury in Rats: Quantification and Implications

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