Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner

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.

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Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2019.00307 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 9

Author(s):

Saef Izzy ◽

Qiong Liu ◽

Zhou Fang ◽

Sevda Lule ◽

Limin Wu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Time Dependent ◽

Transcriptional Networks

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The impact of major depression on outcome following mild-to-moderate traumatic brain injury in older adults

Yearbook of Psychiatry and Applied Mental Health ◽

10.1016/s0084-3970(08)70567-x ◽

2007 ◽

Vol 2007 ◽

pp. 267-268

Author(s):

J.C. Ballenger

Keyword(s):

Older Adults ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Major Depression ◽

Moderate Traumatic Brain Injury ◽

The Impact

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Confirmatory factor structure of the Center for Epidemiologic Studies-Depression scale (CES-D) in mild-to-moderate traumatic brain injury

Brain Injury ◽

10.1080/02699050600676651 ◽

2006 ◽

Vol 20 (5) ◽

pp. 519-527 ◽

Cited By ~ 30

Author(s):

Stephen R. McCauley ◽

Claudia Pedroza ◽

Sharon A. Brown ◽

Corwin Boake ◽

Harvey S. Levin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Factor Structure ◽

Depression Scale ◽

Epidemiologic Studies ◽

Moderate Traumatic Brain Injury ◽

Confirmatory Factor

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Moderate and severe traumatic brain injury: effect of blood alcohol concentration on Glasgow Coma Scale score and relation to computed tomography findings

Journal of Neurosurgery ◽

10.3171/2014.9.jns14322 ◽

2015 ◽

Vol 122 (1) ◽

pp. 211-218 ◽

Cited By ~ 28

Author(s):

Nils Petter Rundhaug ◽

Kent Gøran Moen ◽

Toril Skandsen ◽

Kari Schirmer-Mikalsen ◽

Stine B. Lund ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Injury Severity ◽

Blood Alcohol Concentration ◽

Alcohol Concentration ◽

Dependent Manner ◽

Blood Alcohol ◽

Severe Tbi ◽

Gcs Score ◽

Dose Dependent

OBJECT The influence of alcohol is assumed to reduce consciousness in patients with traumatic brain injury (TBI), but research findings are divergent. The aim of this investigation was to study the effects of different levels of blood alcohol concentration (BAC) on the Glasgow Coma Scale (GCS) scores in patients with moderate and severe TBI and to relate the findings to brain injury severity based on the admission CT scan. METHODS In this cohort study, 265 patients (age range 16–70 years) who were admitted to St. Olavs University Hospital with moderate and severe TBI during a 7-year period were prospectively registered. Of these, 217 patients (82%) had measured BAC. Effects of 4 BAC groups on GCS score were examined with ordinal logistic regression analyses, and the GCS scores were inverted to give an OR > 1. The Rotterdam CT score based on admission CT scan was used to adjust for brain injury severity (best score 1 and worst score 6) by stratifying patients into 2 brain injury severity groups (Rotterdam CT scores of 1–3 and 4–6). RESULTS Of all patients with measured BAC, 91% had intracranial CT findings and 43% had BAC > 0 mg/dl. The median GCS score was lower in the alcohol-positive patients (6.5, interquartile range [IQR] 4–10) than in the alcohol-negative patients (9, IQR 6–13; p < 0.01). No significant differences were found between alcohol-positive and alcohol-negative patients regarding other injury severity variables. Increasing BAC was a significant predictor of lower GCS score in a dose-dependent manner in age-adjusted analyses, with OR 2.7 (range 1.4–5.0) and 3.2 (range 1.5–6.9) for the 2 highest BAC groups (p < 0.01). Subgroup analyses showed an increasing effect of BAC group on GCS scores in patients with Rotterdam CT scores of 1–3: OR 3.1 (range 1.4–6.6) and 6.7 (range 2.7–16.7) for the 2 highest BAC groups (p < 0.01). No such relationship was found in patients with Rotterdam CT scores of 4–6 (p = 0.14–0.75). CONCLUSIONS Influence of alcohol significantly reduced the GCS score in a dose-dependent manner in patients with moderate and severe TBI and with Rotterdam CT scores of 1–3. In patients with Rotterdam CT scores of 4–6, and therefore more CT findings indicating increased intracranial pressure, the brain injury itself seemed to overrun the depressing effect of the alcohol on the CNS. This finding is in agreement with the assumption of many clinicians in the emergency situation.

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