Traumatic Brain Injury Induces a Downregulation of MSK1 in Rat Brain Cortex

Niu, Bo; Li, Zhen; Zhu, Ning; Hou, Gang; Pang, Qi

doi:10.1007/s12031-012-9893-3

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…In our previous study, we found that MSK1 is colocalized with GFAP (Zhong, et al 2018). Previous studies have also reported that MSK1 is colocalized with NeuN and GFAP in brain and spinal cord tissue (Li et al 2013; Ning et al 2013). NeuN is a marker of neurons, and GFAP is a marker of astrocytes.…”

Section: Discussionmentioning

confidence: 80%

“…Recent research has also shown that MSK1 might be involved in SAH and TBI-induced apoptosis. (Ning et al 2013, 2017). However, whether it is related to neuronal apoptosis caused by SCI was not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Although MSK1 is expressed in a variety of tissues, its level is high in immune and neuronal cells. In the CNS (central nervous system), MSK1 is involved in astrocyte inflammation and inhibits the production of inflammatory cytokines (Gong et al 2013); moreover, it might be involved in the pathophysiology of traumatic brain injury (TBI) (Ning et al 2013). MSK1 was also suggested to contribute to SAH (subarachnoid hemorrhage)-induced apoptosis (Ning et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

et al. 2019

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Mitogen- and stress-activated kinase (MSK) 1 is a nuclear serine/threonine kinase. In the central nervous system, it plays an important role in regulating cell proliferation and neuronal survival; it is also involved in astrocyte inflammation and the inhibition of inflammatory cytokine production. However, its specific role in spinal cord injury is not clear. Here, we aimed to elucidate this role using an in vivo animal model. In this study, we found that MSK1 is gradually decreased, starting 1 day after spinal cord injury and to its lowest level 3 days post-injury, after which it gradually increased. To further investigate the possible function of MSK1 in spinal cord injury, we interfered with its expression by utilizing a small interfering RNA (siRNA)-encoding lentivirus, which was injected into the injured spinal cord to inhibit local expression. After MSK1 inhibition, we found that the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were increased. Moreover, the expression of IL-10 was decreased. In addition, neuronal apoptotic cells were increased significantly and expression of the apoptosis-related protein caspase-3 was also increased. Ultrastructural analysis of nerve cells also revealed typical neuronal apoptosis and severe neuronal damage. Finally, we found that hindlimb motor function decreased significantly with MSK1 knockdown. Therefore, our findings suggest that the inhibition of this protein promotes inflammatory responses and apoptosis and suppresses functional recovery after spinal cord injury. MSK1 might thus play an important role in repair after spinal cord injury by regulating inflammation and apoptosis. Electronic supplementary material The online version of this article (10.1007/s12031-019-01298-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

et al. 2019

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“…However, the function and expression of MSK1 in the central nervous system (CNS) have yet to be well-characterized. It is established that MSK1 is highly expressed in the nervous system ( 19 ), but its function is not well understood. In the present study, the expression and distribution of MSK1 in the brain were examined following the experimental induction of SAH in rats.…”

Section: Introductionmentioning

confidence: 99%

MSK1 downregulation is associated with neuronal and astrocytic apoptosis following subarachnoid hemorrhage in rats

et al. 2017

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MSK (mitogen- and stress-activated protein kinase) proteins are a family of mitogen-activated protein kinases. MSKs represent a novel type of pro-survival genes, potentially enhancing the phosphorylation of Bcl2-associated agonist of cell death. However, MSK's function and expression are poorly understood in the central nervous system. In the present study, a subarachnoid hemorrhage (SAH) model was established in SD rats and the expression of MSK1 in the brain subsequent to experimental SAH was investigated. In response to SAH, MSK1 mRNA and protein levels gradually declined, reaching the lowest point at 3 days, and increased thereafter. The expression of active caspase-3 was negatively correlated with MSK1 level. Colocalization and correlating changes in expression of MSK1 and active caspase-3 at neurons and astrocytes indicated that MSK1 downregulation may contribute to SAH-induced apoptosis, validating that MSK1 may be involved in the pathophysiology of the brain cortex subsequent to SAH.

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Predicting changes in cortical electrophysiological function after in vitro traumatic brain injury

Kang

Morrison

2015

Biomech Model Mechanobiol

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Finite element (FE) models of traumatic brain injury (TBI) are capable of predicting injury-induced brain tissue deformation. However, current FE models are not equipped to predict the biological consequences of tissue deformation, which requires the determination of tolerance criteria relating the effects of mechanical stimuli to biologically relevant functional responses. To address this deficiency, we present functional tolerance criteria for the cortex for alterations in neuronal network electrophysiological function in response to controlled mechanical stimuli. Organotypic cortical slice cultures were mechanically injured via equibiaxial stretch with a well-characterized in vitro model of TBI at tissue strains and strain rates relevant to TBI (up to Lagrangian strain of 0.59 and strain rates up to 29 [Formula: see text]. At 4-6 days post-injury, electrophysiological function was assessed simultaneously throughout the cortex using microelectrode arrays. Electrophysiological parameters associated with unstimulated spontaneous network activity (neural event rate, duration, and magnitude), stimulated evoked responses (the maximum response [Formula: see text], the stimulus current necessary for a half-maximal response [Formula: see text], and the electrophysiological parameter [Formula: see text] that is representative of firing uniformity), and evoked paired-pulse ratios at varying interstimulus intervals were quantified for each cortical slice culture. Nonlinear regression was performed between mechanical injury parameters as independent variables (tissue strain and strain rate) and each electrophysiological parameter as output. Parsimonious best-fit equations were determined from a large pool of candidate equations with tenfold cross-validation. Changes in electrophysiological parameters were dependent on strain and strain rate in a complex manner. Compared to the hippocampus, the cortex was less spontaneously active, less excitable, and less prone to significant changes in electrophysiological function in response to controlled deformation (strain or strain rate). Our study provides functional data that can be incorporated into FE models to improve their predictive capabilities of the in vivo consequences of TBI.

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Traumatic Brain Injury Induces a Downregulation of MSK1 in Rat Brain Cortex

Cited by 7 publications

References 20 publications

Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

MSK1 downregulation is associated with neuronal and astrocytic apoptosis following subarachnoid hemorrhage in rats

Predicting changes in cortical electrophysiological function after in vitro traumatic brain injury

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