Early Life Stress Preceding Mild Pediatric Traumatic Brain Injury Increases Neuroinflammation but Does Not Exacerbate Impairment of Cognitive Flexibility during Adolescence

Lajud, Naima; Roque, Angélica; Cheng, Jeffrey P.; Bondi, Corina O.; Kline, Anthony E.

doi:10.1089/neu.2020.7354

Cited by 21 publications

(16 citation statements)

References 84 publications

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“…A follow-up study, using the same model of PMS and TBI, examined cognitive flexibility and thereafter measured proinflammatory cytokines, IL-1β, TNFα, and IL-6 in the prefrontal cortex and hippocampus. Cognitive flexibility was measured using the attentional shift task in early adolescence, whereby mice learned how to discriminate between positive odors and associate this experience with a cue (210,224,225). Mild injury had a significant impact on the first reversal of the attentional shift task.…”

Section: Els + Tbimentioning

confidence: 99%

Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress

et al. 2021

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Despite the high incidence of brain injuries in children, we have yet to fully understand the unique vulnerability of a young brain to an injury and key determinants of long-term recovery. Here we consider how early life stress may influence recovery after an early age brain injury. Studies of early life stress alone reveal persistent structural and functional impairments at adulthood. We consider the interacting pathologies imposed by early life stress and subsequent brain injuries during early brain development as well as at adulthood. This review outlines how early life stress primes the immune cells of the brain and periphery to elicit a heightened response to injury. While the focus of this review is on early age traumatic brain injuries, there is also a consideration of preclinical models of neonatal hypoxia and stroke, as each further speaks to the vulnerability of the brain and reinforces those characteristics that are common across each of these injuries. Lastly, we identify a common mechanistic trend; namely, early life stress worsens outcomes independent of its temporal proximity to a brain injury.

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Section: Els + Tbimentioning

confidence: 99%

Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress

et al. 2021

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“…These clinical-epidemiological data are supported by experimental data in rats: ELS/ACE induce chronic neuro-inflammation [39,40] and oxidative stress concomitant with reduced mitochondrial activity [41]. Acute TBI in addition to pre-traumatic ELS/ACE amplifies microglial activation, neuro-inflammation [42,43], and cortical atrophy [44]. The few available clinical data showed a direct relationship between PTSD severity and changes in cerebral cortex thickness in war veterans with/without ELS/ACE experience [45].…”

Section: Impact Of Chronic Cardiovascular and Psychological Pre-existing Medical Conditions On The Long-term Patient Outcomementioning

confidence: 75%

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide

Merz

McCook

Denoix

et al. 2021

IJMS

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This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid “repayment of the O2 debt” and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC’s) can aggravate the occurrence and severity of complications after trauma. In addition to the “classic” chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC’s, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC’s. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).

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“…However, we cannot exclude the possibility that the ELS‐induced impact on the expression of key regulators of BBB function may result in maladaptation of the BBB specifically in response to other environmental factors. Animal studies clearly show that ELS increases susceptibility to age‐related cognitive decline and neurodegenerative disorders, such as AD and PD, or exacerbates the effects of brain injury (Andersen & Teicher, 2004; Barlow et al., 2007; Catale et al., 2021; Lajud et al., 2021; Llorente et al., 2009; Martisova et al., 2013). Further studies are needed to verify this interesting hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Effects of early‐life stress and sex on blood–brain barrier permeability and integrity in juvenile and adult rats

Solarz

Majcher-Maślanka

Chocyk

2021

Developmental Neurobiology

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Early‐life stress (ELS) is considered a relevant etiological factor for neurodegenerative and mental disorders. In the present study, we hypothesized that ELS may persistently and sex dependently influence blood–brain barrier (BBB) integrity and function during critical periods of brain development and consequently determine susceptibility to and sex‐related prevalence of chronic diseases in adult life. We used the maternal separation (MS) procedure in rats to model ELS and evaluated BBB permeability and gene expression of selected tight junction (TJ) proteins, glucose transporter type 1 (Slc2a1) and aquaporin 4 (Aqp4) in the medial prefrontal cortex (mPFC), dorsal striatum (dSTR) and hippocampus of juvenile and adult rats. Serum concentrations of a peripheral marker of BBB function (S100β) and proinflammatory cytokines were also assessed. We observed developmental sealing of the BBB and sex differences in the permeability of the BBB and the mRNA expression of TJ proteins and Slc2a1. Adult females showed lower BBB permeability and higher levels of Cldn3, Cldn5, Ocln, and Slc2a1 in the mPFC and dSTR than males. MS temporarily increased BBB permeability in the dSTR of juvenile males and affected mRNA expression of the majority of studied proteins related to BBB function in age‐, region‐ and sex‐dependent manners. Additionally, MS sex dependently decreased serum S100β levels and did not affect proinflammatory cytokine concentrations. In general, our study did not reveal a clear or strong negative effect of MS on BBB integrity. However, the results suggest that ELS may induce adaptive/maladaptive changes or compensatory mechanisms within the BBB of unknown yet consequences.

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Early Life Stress Preceding Mild Pediatric Traumatic Brain Injury Increases Neuroinflammation but Does Not Exacerbate Impairment of Cognitive Flexibility during Adolescence

Cited by 21 publications

References 84 publications

Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress

Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide

Effects of early‐life stress and sex on blood–brain barrier permeability and integrity in juvenile and adult rats

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