Modulating chronic outcomes after pediatric traumatic brain injury: Distinct effects of social and environmental enrichment

Dill, Larissa K.; Teymornejad, Sadaf; Sharma, Rishabh; Bozkurt, Salome; Christensen, Jennaya; Chu, Erskine; Rewell, Sarah S J; Shad, Ali; Mychasiuk, Richelle; Semple, Bridgette D.

doi:10.1016/j.expneurol.2023.114407

Cited by 9 publications

(4 citation statements)

References 98 publications

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“…Environmental enrichment increased sensorimotor performance and sociosexual interactions, while social housing reduced hyperactivity and anxiety-like behaviors. [ 25 ] Similarly, other reports of rats placed in an enriched environment for 15 days before inducing a prefrontal cortical injury demonstrated that environmental enrichment preexposure led to improved spatial memory recovery and reduced sensory neglect following TBI. [ 50 ]…”

Section: Lifestyle-based Interventionsmentioning

confidence: 90%

The importance of behavioral interventions in traumatic brain injury

Buccilli,

Alan,

Baha’

et al. 2024

Surgical Neurology International

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Background: Traumatic brain injury (TBI) poses a significant public health concern, profoundly impacting individuals and society. In this context, behavioral interventions have gained prominence as crucial elements in TBI management, addressing the diverse needs of TBI-affected individuals. Methods: A comprehensive literature search was conducted, utilizing databases such as PubMed, Embase, and Scopus. Inclusion criteria encompassed studies focusing on behavioral interventions in TBI, with a particular emphasis on their impact on outcomes. Relevant articles published within the past decade were prioritized, and a qualitative synthesis of the findings was performed. Results: Behavioral interventions have demonstrated their effectiveness in addressing various aspects of TBI care. They have been instrumental in improving cognitive functions, emotional stability, and adaptive behaviors among TBI patients. However, it is important to acknowledge that challenges still exist, including issues related to clinical heterogeneity and healthcare disparities. Conclusion: The integration of behavioral interventions into standard clinical practice marks a transformative shift in TBI care. This approach holds immense potential for enhancing patient outcomes and elevating the overall quality of life for individuals grappling with the complexities of this condition. This review serves as a clarion call for healthcare practitioners, researchers, and policymakers to recognize the pivotal role of behavioral interventions in TBI care, advocating for their wider adoption to advance the field toward a more holistic and patient-centric approach.

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Section: Lifestyle-based Interventionsmentioning

confidence: 90%

The importance of behavioral interventions in traumatic brain injury

Buccilli,

Alan,

Baha’

et al. 2024

Surgical Neurology International

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“…On days 1 and 2 of testing, motor function was assessed with the accelerating rotarod (30 mm diameter rod, four lanes 50 mm wide each, divided by 100 mm tall partitions; Panlab/ Harvard Apparatus, Holliston, MA, USA) as previously described [ 29 , 64 ]. This consisted of one day of training and one test day, with a total of 3 trials per day and an inter-trial interval of 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…The three-chamber social test (3CT) was used to assess sociability, social exploration, social memory and social preference behaviors. As previously described [ 29 , 64 ], this assessment was conducted over three consecutive 10-min stages per mouse and mice were single-housed 24 h prior to 3CT testing to promote sociability during the completion of this task. Stimulus mice used were strain, sex- and aged-matched to experimental mice, and sourced from the same in-house C57BL/6 J (Jax) colony.…”

Section: Methodsmentioning

confidence: 99%

A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice

Baker,

Wright,

Uboldi

et al. 2024

J Neuroinflammation

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Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity—all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.

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“…General locomotor activity was assessed using an open-field test (400 mm W × 400 mm D × 300 mm H) (10 min duration), with anxiety as a secondary measure based on time spent in the center area compared to the periphery of the arena [43]. Gross motor functioning and coordination were assessed using the accelerating rotarod test, averaged across 3 trials per day (with a 30 min inter-trial interval) over two consecutive days, with the rotarod accelerating from 4 to 40 rpm over a 5 min period [44,45]. Working and spatial memory was evaluated using the Y-maze (15 min habitation, 30 min inter-trial interval, followed by 5 min test phase) as previously described [42], and analyzed using the discrimination index (Discrimination index = Time Novel −Time Familiar Time Novel +Time Familiar ).…”

Section: Behavior Testingmentioning

confidence: 99%

Regulation of Microglial Signaling by Lyn and SHIP-1 in the Steady-State Adult Mouse Brain

Chu,

Mychasiuk,

Tsantikos

et al. 2023

Cells

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Chronic neuroinflammation and glial activation are associated with the development of many neurodegenerative diseases and neuropsychological disorders. Recent evidence suggests that the protein tyrosine kinase Lyn and the lipid phosphatase SH2 domain-containing inositol 5′ phosphatase-1 (SHIP-1) regulate neuroimmunological responses, but their homeostatic roles remain unclear. The current study investigated the roles of Lyn and SHIP-1 in microglial responses in the steady-state adult mouse brain. Young adult Lyn−/− and SHIP-1−/− mice underwent a series of neurobehavior tests and postmortem brain analyses. The microglial phenotype and activation state were examined by immunofluorescence and flow cytometry, and neuroimmune responses were assessed using gene expression analysis. Lyn−/− mice had an unaltered behavioral phenotype, neuroimmune response, and microglial phenotype, while SHIP-1−/− mice demonstrated reduced explorative activity and exhibited microglia with elevated activation markers but reduced granularity. In addition, expression of several neuroinflammatory genes was increased in SHIP-1−/− mice. In response to LPS stimulation ex vivo, the microglia from both Lyn−/− and SHIP-1−/− showed evidence of hyper-activity with augmented TNF-α production. Together, these findings demonstrate that both Lyn and SHIP-1 have the propensity to control microglial responses, but only SHIP-1 regulates neuroinflammation and microglial activation in the steady-state adult brain, while Lyn activity appears dispensable for maintaining brain homeostasis.

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Modulating chronic outcomes after pediatric traumatic brain injury: Distinct effects of social and environmental enrichment

Cited by 9 publications

References 98 publications

The importance of behavioral interventions in traumatic brain injury

The importance of behavioral interventions in traumatic brain injury

A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice

Regulation of Microglial Signaling by Lyn and SHIP-1 in the Steady-State Adult Mouse Brain

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