Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: A preliminary study

Su, Shao-Hua; Xu, Wei; Li, Ming; Zhang, Lin; Wu, Yuankui; Yu, Fei; Hai, Jian

doi:10.1016/j.bbi.2014.01.009

Cited by 69 publications

(72 citation statements)

References 48 publications

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“…As previously discussed, heightened levels of systemic inflammatory markers are indicative of worse outcomes following TBI, even those considered mild 122 . Therefore, in this conceptual model, we postulate that the GBMAx may be a therapeutic target to attenuate this systemic inflammatory response to augment recovery in the acute and/or subacute phases following the head injury ( Figure 2).…”

Section: Potential Clinical Implicationsmentioning

confidence: 88%

Section: "Bottom-up": Potential Gut-to-brain Signalingmentioning

confidence: 92%

“…Notably, the LPS-induced systemic inflammatory cytokines that are elevated by experimental endotoxemia and thought to provoke "sickness behavior" are the same inflammatory markers previously found to be predictive of a worse outcome following TBI 122 . Su and colleagues report that elevated levels of CRP, which is indicative of systemic inflammation, at 1, 2, and 3 months after a mild TBI was significantly correlated with persistent neuropsychological symptoms 122 . Of particular note, the typical symptoms of sickness behavior following injections of LPS in models of experimental endotoxemia shares considerable overlap with a constellation of symptoms often referred "post-concussion syndrome (PCS)" 71,123,124 .…”

Section: "Bottom-up": Potential Gut-to-brain Signalingmentioning

confidence: 92%

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

155

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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Section: Potential Clinical Implicationsmentioning

confidence: 88%

Section: "Bottom-up": Potential Gut-to-brain Signalingmentioning

confidence: 92%

Section: "Bottom-up": Potential Gut-to-brain Signalingmentioning

confidence: 92%

See 1 more Smart Citation

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

155

103

View full text Add to dashboard Cite

show abstract

“…In addition, coated platelet levels remain elevated in patients who had mTBI for an extended period, potentially up to 9 years, suggesting long-term inflammatory consequences (Prodan et al, 2013). In addition, elevation of C-reactive protein (CRP), a biomarker of systemic inflammation, at baseline predicted persistent PCS symptoms, cognitive impairment and psychological problems at 3 months after mTBI (Su et al, 2014).…”

Section: The Role Of Neuroinflammationmentioning

confidence: 99%

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

Rathbone

Tharmaradinam

Jiang

et al. 2015

Brain, Behavior, and Immunity

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“…In fact, by Su et al identified a significant association between continued elevated CRP levels and increased the incidence of PCS (OR ¼ 2.719; CI 95%: 1.609-4.594) in 213 patients with mTBI. 82 Essentially, among this cohort of patients, persistent higher CRP levels forecasted clinically relevant cognitive impairment.…”

Section: Studies Of Tbi and Inflammatory Responsesmentioning

confidence: 99%

Effects of concussion on the blood–brain barrier in humans and rodents

Sahyouni

Gutierrez

Gold

et al. 2017

Journal of Concussion

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Traumatic brain injury and the long-term consequences of repeated concussions constitute mounting concerns in the United States, with 5.3 million individuals living with a traumatic brain injury-related disability. Attempts to understand mechanisms and possible therapeutic approaches to alleviate the consequences of repeat mild concussions or traumatic brain injury on cerebral vasculature depend on several aspects of the trauma, including: (1) the physical characteristics of trauma or insult that result in damage; (2) the time ''window'' after trauma in which neuropathological features develop; (3) methods to detect possible breakdown of the blood-brain barrier; and (4) understanding different consequences of a single concussion as compared with multiple concussions. We review the literature to summarize the current understanding of blood-brain barrier and endothelial cell changes post-neurotrauma in concussions and mild traumatic brain injury. Attention is focused on concussion and traumatic brain injury in humans, with a goal of pointing out the gaps in our knowledge and how studies of rodent model systems of concussion may help in filling these gaps. Specifically, we focus on disruptions that concussion causes to the blood-brain barrier and its multifaceted consequences. Importantly, the magnitude of post-concussion blood-brain barrier dysfunction may influence the time course and extent of neuronal recovery; hence, we include in this review comparisons of more severe traumatic brain injury to concussion where appropriate. Finally, we address the important, and still unresolved, issue of how best to detect possible breakdown in the blood-brain barrier following neurotrauma by exploring intravascular tracer injection in animal models to examine leakage into the brain parenchyma.

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Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: A preliminary study

Cited by 69 publications

References 48 publications

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

Effects of concussion on the blood–brain barrier in humans and rodents

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