scholarly journals Greater neurodegeneration and behavioral deficits after single closed head traumatic brain injury in adolescent vs adult mice

2019 ◽  
Author(s):  
Fernanda Guilhaume-Correa ◽  
Shelby M. Cansler ◽  
Emily M. Shalosky ◽  
Michael D. Goodman ◽  
Nathan K. Evanson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Recognition Performance ◽  
Memory Performance ◽  
Health Concern ◽  
Post Injury ◽  
Adult Mice ◽  
Closed Head ◽  
Old Adult ◽  
Hippocampal Neurodegeneration

AbstractIntroductionTraumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year, of which about 1 million are children under 19 years old. Animal models of TBI have been developed and used in multiple ages of animals, but direct comparisons of adult and adolescent populations are rare. The current studies were undertaken to directly compare outcomes between adult and adolescent mice, using a closed head, single impact model of TBI.MethodsSix-week-old adolescent and 9-week-old adult male mice were subjected to TBI using a closed head weight drop model. Histological measures for neurodegeneration, gliosis, and microglial neuroinflammation, and behavioral tests of locomotion and memory were performed.ResultsAdolescent TBI mice have increased mortality (X2= 20.72, p < 0.001) compared to adults. There is also evidence of hippocampal neurodegeneration in adolescents, but not adults. Presence of hippocampal neurodegeneration correlates with histologic activation of microglia, but not with increased markers of astrogliosis. Adults and adolescents have similar locomotion deficits after TBI that recover by 16 days post-injury. Adolescents have memory deficits as evidenced by impaired novel object recognition performance 3 and 16 days post injury (F1,26 = 5.23, p = 0.031) while adults do not.ConclusionsAdults and adolescents within a close age range (6-9 weeks) respond to TBI differently. Adolescents are more severely affected by mortality, neurodegeneration, and inflammation in the hippocampus compared to adults. Adolescents, but not adults, have worse memory performance after TBI that lasts up to 16 days post injury.

scholarly journals 3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 8276
Author(s):  
Pen-Sen Huang ◽  
Ping-Yen Tsai ◽  
Ling-Yu Yang ◽  
Daniela Lecca ◽  
Weiming Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Short Term Memory ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Cognitive Behaviors ◽  
Moderate Traumatic Brain Injury ◽  
Short And Long Term ◽  
Behavioral Impairments ◽  
Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

scholarly journals Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches?

2022 ◽  
Vol 11 (2) ◽  
pp. 358
Author(s):  
Francesco Latini ◽  
Markus Fahlström ◽  
Fredrik Vedung ◽  
Staffan Stensson ◽  
Elna-Marie Larsson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Global Analysis ◽  
Memory Performance ◽  
Regional Analysis ◽  
Long Term Memory ◽  
Post Injury ◽  
White Matter Changes

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Duration of post-traumatic amnesia is uniquely associated with memory functioning in chronic moderate-to-severe traumatic brain injury

2021 ◽  
pp. 1-13
Author(s):  
Umesh M. Venkatesan ◽  
Amanda R. Rabinowitz ◽  
Stephanie J. Wolfert ◽  
Frank G. Hillary
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Memory Performance ◽  
Acute Injury ◽  
Post Injury ◽  
Memory Processing ◽  
Memory Functioning ◽  
Traumatic Amnesia ◽  
Post Traumatic ◽  
With Memory

BACKGROUND: Disrupted memory circuitry may contribute to post-traumatic amnesia (PTA) after traumatic brain injury (TBI). It is unclear whether duration of PTA (doPTA) uniquely impacts memory functioning in the chronic post-injury stage. OBJECTIVE: To examine the relationship between doPTA and memory functioning, independent of other cognitive abilities, in chronic moderate-to-severe TBI. METHODS: Participants were 82 individuals (median chronicity = 10.5 years) with available doPTA estimates and neuropsychological data. Composite memory, processing speed (PS), and executive functioning (EF) performance scores, as well as data on subjective memory (SM) beliefs, were extracted. DoPTA-memory associations were evaluated via linear modeling of doPTA with memory performance and clinical memory status (impaired/unimpaired), controlling for PS, EF and demographic covariates. Interrelationships between doPTA, objective memory functioning, and SM were assessed. RESULTS: DoPTA was significantly related to memory performance, even after covariate adjustment. Impairment in memory, but not PS or EF, was associated with a history of longer doPTA. SM was associated with memory performance, but unrelated to doPTA. CONCLUSIONS: Findings suggest a specific association between doPTA—an acute injury phenomenon—and chronic memory deficits after TBI. Prospective studies are needed to understand how underlying mechanisms of PTA shape distinct outcome trajectories, particularly functional abilities related to memory processing.

scholarly journals Up-regulation of Wnt/β-catenin expression is accompanied with vascular repair after traumatic brain injury

2017 ◽  
Vol 38 (2) ◽  
pp. 274-289 ◽  
Author(s):  
Arjang Salehi ◽  
Amandine Jullienne ◽  
Mohsen Baghchechi ◽  
Mary Hamer ◽  
Mark Walsworth ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Repair Process ◽  
Cerebral Vasculature ◽  
Vascular Repair ◽  
Post Injury ◽  
Injury Site ◽  
Transgenic Mouse Line ◽  
Adult Mice

Recent data suggest that repairing the cerebral vasculature after traumatic brain injury (TBI) may help to improve functional recovery. The Wnt/β-catenin signaling pathway promotes blood vessel formation during vascular development, but its role in vascular repair after TBI remains elusive. In this study, we examined how the cerebral vasculature responds to TBI and the role of Wnt/β-catenin signaling in vascular repair. We induced a moderate controlled cortical impact in adult mice and performed vessel painting to visualize the vascular alterations in the brain. Brain tissue around the injury site was assessed for β-catenin and vascular markers. A Wnt transgenic mouse line was utilized to evaluate Wnt gene expression. We report that TBI results in vascular loss followed by increases in vascular structure at seven days post injury (dpi). Immature, non-perfusing vessels were evident in the tissue around the injury site. β-catenin protein expression was significantly reduced in the injury site at 7 dpi. However, there was an increase in β-catenin expression in perilesional vessels at 1 and 7 dpi. Similarly, we found increased number of Wnt-GFP-positive vessels after TBI. Our findings suggest that Wnt/β-catenin expression contributes to the vascular repair process after TBI.

scholarly journals Validation and standardization of a new radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

2020 ◽  
Author(s):  
Teresa Macheda ◽  
Kelly N. Roberts ◽  
Adam D. Bachstetter
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Learning And Memory ◽  
Water Maze ◽  
Cognitive Impairments ◽  
Memory Performance ◽  
Closed Head Injury ◽  
Therapeutic Interventions ◽  
Test Procedures ◽  
Closed Head

AbstractCognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and pathology, as well as when pharmacological approaches are used.

SURVEY IN SERUM ADH CONCENTRATION IN TRAUMATIC BRAIN INJURY PATIENTS

2014 ◽  
pp. 83-89
Author(s):  
Dung Ngo ◽  
Thi Nhan Nguyen ◽  
Khanh Hoang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Osmotic Pressure ◽  
Negative Correlation ◽  
Closed Head Injury ◽  
Serum Levels ◽  
Sodium Concentration ◽  
Plasma Sodium ◽  
Plasma Sodium Concentration ◽  
Closed Head

Objective: Study on 106 patients with closed head injury, assessment of serum ADH concentration, correlation with Glasgow score, sodium and plasma osmotic pressure. Patients and methods: Patients with closed head injuries were diagnosed determined by computerized tomography, admitted to the Hue Central Hospital 72 hours ago. Results: (i) Serum concentration of ADH 42.21 ± 47.80 pg/ml. (ii) There is a negative correlation between serum levels of ADH with: (1) Glasgow point r = -0.323, p <0.01; (2) Plasma sodium concentration r = - 0.211, p > 0.05; (3) Plasma osmotic pressure r = - 0.218, p> 0.05. Conclusion: There is a negative correlation between serum levels of ADH with Glasgow scale, plasma sodium concentration and osmotic pressure in plasma. Key words: ADH traumatic brain injury.

scholarly journals Longitudinal Growth Curve Trajectories of Family Dynamics after Pediatric Traumatic Brain Injury in Mexico

2020 ◽  
Vol 17 (22) ◽  
pp. 8508
Author(s):  
Grace B. McKee ◽  
Laiene Olabarrieta-Landa ◽  
Paula K. Pérez-Delgadillo ◽  
Ricardo Valdivia-Tangarife ◽  
Teresita Villaseñor-Cabrera ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Family Functioning ◽  
Growth Curve ◽  
Family Members ◽  
Family Satisfaction ◽  
Health Concern ◽  
Pediatric Traumatic Brain Injury ◽  
Large Hospital ◽  
Pediatric Tbi

Pediatric traumatic brain injury (TBI) represents a serious public health concern. Family members are often caregivers for children with TBI, which can result in a significant strain on familial relationships. Research is needed to examine aspects of family functioning in the context of recovery post-TBI, especially in Latin America, where cultural norms may reinforce caregiving by family members, but where resources for these caregivers may be scarce. This study examined caregiver-reported family satisfaction, communication, cohesion, and flexibility at three time points in the year post-injury for 46 families of a child with TBI in comparison to healthy control families. Families experiencing pediatric TBI were recruited from a large hospital in Guadalajara, Mexico, while healthy controls were recruited from a local educational center. Results from multilevel growth curve models demonstrated that caregivers of children with a TBI reported significantly worse family functioning than controls at each assessment. Families experiencing pediatric TBI were unable to attain the level of functioning of controls during the time span studied, suggesting that these families are likely to experience long-term disruptions in family functioning. The current study highlights the need for family-level intervention programs to target functioning for families affected by pediatric TBI who are at risk for difficulties within a rehabilitation context.

scholarly journals A-126 Clinical Utility of Risk Factors to Predict Self-reported Neurobehavioral Outcome Following Traumatic Brain Injury: PTSD, Sleep, Resilience, and Lifetime Blast Exposure

2020 ◽  
Vol 35 (6) ◽  
pp. 919-919
Author(s):  
Lange R ◽  
Lippa S ◽  
Hungerford L ◽  
Bailie J ◽  
French L ◽  
...  
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Risk Factor ◽  
Brain Injury ◽  
Clinical Utility ◽  
Poor Sleep ◽  
Post Injury ◽  
Poor Outcome ◽  
Blast Exposure ◽  
Neurobehavioral Outcome

Abstract Objective To examine the clinical utility of PTSD, Sleep, Resilience, and Lifetime Blast Exposure as ‘Risk Factors’ for predicting poor neurobehavioral outcome following traumatic brain injury (TBI). Methods Participants were 993 service members/veterans evaluated following an uncomplicated mild TBI (MTBI), moderate–severe TBI (ModSevTBI), or injury without TBI (Injured Controls; IC); divided into three cohorts: (1) &lt; 12 months post-injury, n = 237 [107 MTBI, 71 ModSevTBI, 59 IC]; (2) 3-years post-injury, n = 370 [162 MTBI, 80 ModSevTBI, 128 IC]; and (3) 10-years post-injury, n = 386 [182 MTBI, 85 ModSevTBI, 119 IC]. Participants completed a 2-hour neurobehavioral test battery. Odds Ratios (OR) were calculated to determine whether the ‘Risk Factors’ could predict ‘Poor Outcome’ in each cohort separately. Sixteen Risk Factors were examined using all possible combinations of the four risk factor variables. Poor Outcome was defined as three or more low scores (&lt; 1SD) on five TBI-QOL scales (e.g., Fatigue, Depression). Results In all cohorts, the vast majority of risk factor combinations resulted in ORs that were ‘clinically meaningful’ (ORs &gt; 3.00; range = 3.15 to 32.63, all p’s &lt; .001). Risk factor combinations with the highest ORs in each cohort were PTSD (Cohort 1 & 2, ORs = 17.76 and 25.31), PTSD+Sleep (Cohort 1 & 2, ORs = 18.44 and 21.18), PTSD+Sleep+Resilience (Cohort 1, 2, & 3, ORs = 13.56, 14.04, and 20.08), Resilience (Cohort 3, OR = 32.63), and PTSD+Resilience (Cohort 3, OR = 24.74). Conclusions Singularly, or in combination, PTSD, Poor Sleep, and Low Resilience were strong predictors of poor outcome following TBI of all severities and injury without TBI. These variables may be valuable risk factors for targeted early interventions following injury.

scholarly journals Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 500
Author(s):  
William Brad Hubbard ◽  
Meenakshi Banerjee ◽  
Hemendra Vekaria ◽  
Kanakanagavalli Shravani Prakhya ◽  
Smita Joshi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Closed Head Injury ◽  
Diffuse Brain Injury ◽  
Blood Brain ◽  
Closed Head ◽  
Leukocyte Counts ◽  
Neutrophil Aggregation ◽  
Blood Leukocyte

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis.

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