scholarly journals Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury

2018 ◽  
Vol 129 (5) ◽  
pp. 1295-1304 ◽  
Author(s):  
Yanlu Zhang ◽  
Michael Chopp ◽  
Zheng Gang Zhang ◽  
Yi Zhang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dose Response ◽  
Rat Model ◽  
Functional Outcomes ◽  
Cognitive Outcome ◽  
Dose Effect ◽  
Functional Improvement ◽  
Controlled Study ◽  
Cognitive Recovery

OBJECTIVECerebrolysin is a neuropeptide preparation that mimics the properties of neurotrophic factors and has had beneficial effects in the treatment of neurodegenerative diseases, stroke, and traumatic brain injury (TBI). To further evaluate treatment schemes, the authors assessed the dose-response of Cerebrolysin on functional improvement in a rat model of mild TBI (mTBI).METHODSThis dose-response study was a prospective, randomized, blinded, and placebo-controlled preclinical experiment. Male Wistar adult rats, subjected to mTBI induced by a closed head impact, were treated randomly with 0 (saline as placebo), 0.8, 2.5, or 7.5 ml/kg of Cerebrolysin 4 hours after mTBI and daily for a total of 10 consecutive days. A battery of cognitive and sensorimotor functional tests was performed over 90 days.RESULTSThe primary outcome was functional improvement over the 90 days; animal weight and death were the secondary and safety outcomes, respectively. A significant (p < 0.001) dose effect of Cerebrolysin on cognitive recovery 3 months after injury was found. Cerebrolysin at a dose of ≥ 0.8 ml/kg significantly (p < 0.001) improved cognitive outcome. The higher dose (7.5 ml/kg) resulted in significantly better cognitive recovery than the lowest doses (0.8 ml/kg) but not relative to the 2.5-ml/kg dose. Cerebrolysin at a dose of 2.5 or 7.5 ml/kg also caused different onset times of significant improvement in sensorimotor function. No differences in body weight or mortality rate among the groups were found.CONCLUSIONSThis preclinical randomized, placebo-controlled, and blinded study with a clinically relevant treatment scheme revealed that Cerebrolysin at doses of 0.8–7.5 ml/kg, administered 4 hours after mTBI and then once daily for a total of 10 consecutive days, improved functional outcomes 3 months after injury. A dose of 2.5 ml/kg is likely an optimal dose for the treatment of experimental mTBI.

scholarly journals Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury

Neurosurgery ◽  
2005 ◽  
Vol 56 (3) ◽  
pp. 590-604 ◽  
Author(s):  
Jonas J. Gopez ◽  
Hongfei Yue ◽  
Ram Vasudevan ◽  
Amir S. Malik ◽  
Lester N. Fogelsanger ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Functional Outcomes ◽  
Specific Inhibitor ◽  
Cyclooxygenase 2

The Effect of Early Rehabilitation Intervention on Functional Outcome in Patients with Traumatic Brain Injury: A Systematic Review Protocol

2020 ◽  
Author(s):  
Hamidreza khankeh ◽  
Mohammad Eghbali ◽  
Sayed Ali Hosseini ◽  
Vafa Rahimi-Movaghar
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcomes ◽  
Meta Analysis ◽  
Early Rehabilitation ◽  
Functional Improvement ◽  
Factors Affecting ◽  
Review Protocol ◽  
Review Study

Abstract Introduction: Traumatic Brain Injury (TBI) is a serious health problem which is considered as a silent epidemic. Early rehabilitation interventions are among significant factors affecting the functional improvement, reduction of disability and impairment in patients. Initial observations indicate evidence for the effectiveness of such interventions; however, there is no related systematic review study conducted so far. The main objective of the present study is to investigate the prevalence of the interventions and to determine the effectiveness of such interventions on functional outcomes for patients with TBI. Methodology: In order to find related studies, several data bases such as Embase, Medline, Scopus, PubMed and Web of Science and also Gray Literature are observed. Inclusion and exclusion criteria are designed and modified by a team of experts. Observation of the content of the titles and abstracts will be done by two reviewers and then the data will be extracted and evaluated. All the studies published in English between 1990 and 2019 were included. Primary outcomes include the frequency of early rehabilitation interventions and the effects of such interventions on functional outcomes. If possible, meta-analysis will be conducted as well. Discussion: The results of this systematic review study will contribute to identification and clarification of different types of rehabilitation interventions and the effects of such interventions on TBI patients’ functional outcomes.

scholarly journals A Pilot Project of Early Integrated Traumatic Brain Injury Rehabilitation in Singapore

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Siew Kwaon Lui ◽  
Yee Sien Ng ◽  
Annie Jane Nalanga ◽  
Yeow Leng Tan ◽  
Chek Wai Bok
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcomes ◽  
Inpatient Rehabilitation ◽  
Epidemiological Data ◽  
Pilot Project ◽  
Functional Improvement ◽  
Early Screening ◽  
Neurosurgical Department ◽  
Rehabilitation Team

Objective.Document acute neurosurgical and rehabilitation parameters of patients of all traumatic brain injury (TBI) severities and determine whether early screening along with very early integrated TBI rehabilitation changes functional outcomes.Methods. Prospective study involving all patients with TBI admitted to a neurosurgical department of a tertiary hospital. They were assessed within 72 hours of admission by the rehabilitation team and received twice weekly rehabilitation reviews. Patients with further rehabilitation needs were then transferred to the attached acute inpatient TBI rehabilitation unit (TREATS) and their functional outcomes were compared against a historical group of patients. Demographic variables, acute neurosurgical characteristics, medical complications, and rehabilitation outcomes were recorded.Results.There were 298 patients screened with an average age of61.8±19.1years. The most common etiology was falls (77.5%). Most patients were discharged home directly (67.4%) and 22.8% of patients were in TREATS. The TREATS group functionally improved (P<0.001). Regression analysis showed by the intervention of TREATS, that there was a statistically significant FIM functional gain of 18.445 points (95% CI −30.388 to −0.6502,P=0.03).Conclusion.Our study demonstrated important epidemiological data on an unselected cohort of patients with TBI in Singapore and functional improvement in patients who further received inpatient rehabilitation.

scholarly journals Demographics of traumatic brain injury and outcomes of continuous chain of early rehabilitation in Singapore

2020 ◽  
Vol 29 (1) ◽  
pp. 33-41
Author(s):  
Siew Kwaon Lui ◽  
Stephanie Man Chung Fook-Chong ◽  
Qiao Qi Teo
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcomes ◽  
Functional Independence ◽  
Functional Improvement ◽  
Clinical Predictors ◽  
Early Screening ◽  
Negatively Associated ◽  
Continuous Chain ◽  
Neurosurgical Intervention

Background: Evidence shows that early initiation of a continuous chain of rehabilitation is associated with better functional outcomes in traumatic brain injured patients. The Department of Rehabilitation Medicine initiated early screening and review of patients with all traumatic brain injury (TBI) severity within 72 hours of acute admission, followed by direct transfer of suitable patients to acute inpatient rehabilitation (AIR). Objectives: This study aim to document the demographics and clinical characteristics of all TBI patients admitted to the local acute hospital; determine the characteristics of patients with TBI who are directly transferred to AIR following early screening and review; and determine clinical predictors affecting functional outcomes of patients of all TBI severity. Methods: A total of 491 patients were screened and reviewed; 116 patients were directly transferred to AIR. Results: The median age of the screened cohort was 67.0 years (interquartile range 50.0–77.0 years). Falls were the leading mechanism of TBI. Infection (odds ratio (OR)=2.95, 95% confidence interval (CI) 1.59–5.49) and neurosurgical intervention (OR=2.18, 95% CI 1.24–3.81) increased the odds of transfer to AIR. The Functional Independence Measure (FIM) gain after receiving AIR was significant ( p<0.001). Increased age, complications, high motor admission FIM (AFIM) and long rehabilitation length of stay (RLOS) were negatively associated with FIM gain and FIM efficiency. Conclusions: Our study demonstrated that falls were the leading mechanism of TBI, with the majority of patients being older. Infection and neurosurgical intervention increased the likelihood of transfer to AIR. There was functional improvement after AIR. Age, complications, motor AFIM and RLOS were negatively associated with FIM gain and FIM efficiency. Further local research is warranted to confirm these findings.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

Temporal profile and utility of serum neurofilament light in a rat model of mild traumatic brain injury

2021 ◽  
Vol 341 ◽  
pp. 113698
Author(s):  
William T. O'Brien ◽  
Louise Pham ◽  
Rhys D. Brady ◽  
Jesse Bain ◽  
Glenn R. Yamakawa ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Rat Model ◽  
Neurofilament Light ◽  
Temporal Profile

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans

2020 ◽  
pp. 1-7
Author(s):  
Sara M. Lippa ◽  
Jessica Gill ◽  
Tracey A. Brickell ◽  
Louis M. French ◽  
Rael T. Lange
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Outcome ◽  
Service Members ◽  
Neurocognitive Performance ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Blood Draw ◽  
Neurofilament Light ◽  
History Of

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

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