scholarly journals The Effect of Oral Mucosal Mesenchymal Stem Cells on Long-Term Brain Edema and Lesion, Anxiety-Like Behavior, and Cognitive and Motor Outcomes in Experimental Traumatic Brain Injury

2020 ◽  
Author(s):  
Fatemeh Dehghanian ◽  
Zahra Soltani ◽  
Alireza Farsinejad ◽  
Elham Jafari ◽  
Hamideh Bashiri
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Brain Edema ◽  
Cognitive Outcomes ◽  
Motor Impairments ◽  
Novel Approach ◽  
New Treatment

Abstract In recent years, the use of mesenchymal stem cells as a novel approach in the treatment of neurodegenerative diseases including traumatic brain injury has been proposed. In this study, the effect of oral mucosal mesenchymal stem cells (OMSCs) on traumatic brain injury was evaluated in long-term. Animals were divided into 4 groups including sham, TBI, vehicle (Veh) and stem cell (SC). Brain damage was induced by the Marmarou’s method. The number of 2 × 106 OMSCs was intravenously injected 1 and 24 hours after the injury. Brain edema and pathological outcome were assessed at 24 hours and 21 days after the injury. Besides, long-term neurological, motor and cognitive outcomes were evaluated at days 3, 7, 14, and 21 after the injury. inflammation (P < 0.01), reduce axonal damage (P < 0.01, P < 0.05; respectively) and prevent microglia proliferation (P < 0.05, P < 0.01; respectively) at 24 h and 21 days after the injury. Neurological function improvement (P < 0.001), memory enhancement (P < 0.05), anxiety-like behavior reduction (P < 0.001) and motor function amelioration (P < 0.05, P < 0.001, P < 0.01, P < 0.05; respectively) at days of 3, 7, 14, 21 after the injury were observed in the treatment group. According to the results of this study, OMSCs administration after TBI reduced brain edema and inflammation, and improved neurologic, memory and motor impairments, and anxiety-like behavior in long-term. Therefore, OMSCs could be a promising and new treatment option for TBI in the future.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

scholarly journals Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury

2020 ◽  
Author(s):  
Anna Badner ◽  
Emily K. Reinhardt ◽  
Theodore V. Nguyen ◽  
Nicole Midani ◽  
Andrew T. Marshall ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Spatial Learning ◽  
Risk Taking ◽  
Mechanisms Of Action ◽  
Human Neural Stem Cells ◽  
Risk Taking Behavior

AbstractHuman neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105 freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.

306 GCS Does Not Predict Cognitive Outcome 30 Years After Severe Traumatic Brain Injury

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 264-265
Author(s):  
Molly E Hubbard ◽  
Abdullah Bin Zahid ◽  
Gabrielle Meyer ◽  
Kathleen Vonderhaar ◽  
David Y Balser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Assessment Tool ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Symptom Severity Score ◽  
History Of ◽  
Severe Tbi

Abstract INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available. METHODS Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression. RESULTS >45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points. CONCLUSION Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.

Potential application of an injectable hydrogel scaffold loaded with mesenchymal stem cells for treating traumatic brain injury

2018 ◽  
Vol 6 (19) ◽  
pp. 2982-2992 ◽  
Author(s):  
Kun Zhang ◽  
Zhenqing Shi ◽  
Jiankang Zhou ◽  
Qu Xing ◽  
Shanshan Ma ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Brain Injury ◽  
Sodium Alginate ◽  
Potential Application ◽  
Hydrogel Scaffold ◽  
Injectable Hydrogel ◽  
Tissue Scaffold

In this contribution, we developed an injectable hydrogel composed of sodium alginate and hyaluronic acid that acts as a tissue scaffold to create a more optimal microenvironment for the stem cells for potential application of traumatic brain injury implantation.

scholarly journals Engineered Mesenchymal Stem Cells with Enhanced Tropism and Paracrine Secretion of Cytokines and Growth Factors to Treat Traumatic Brain Injury

Stem Cells ◽  
2015 ◽  
Vol 33 (2) ◽  
pp. 456-467 ◽  
Author(s):  
Zhe Wang ◽  
Yu Wang ◽  
Zhiyong Wang ◽  
J. Silvio Gutkind ◽  
Zhongliang Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Brain Injury ◽  
Paracrine Secretion

Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model

2013 ◽  
Vol 33 (7) ◽  
pp. 673-684 ◽  
Author(s):  
D Torrente ◽  
MF Avila ◽  
R Cabezas ◽  
L Morales ◽  
J Gonzalez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Wound Closure ◽  
Human Mesenchymal Stem Cells ◽  
Neuronal Population ◽  
Paracrine Factors ◽  
Neuroprotective Strategy

Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury.

scholarly journals Interactome and reciprocal activation of pathways in topical mesenchymal stem cells and the recipient cerebral cortex following traumatic brain injury

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ping K. Lam ◽  
Kevin K. W. Wang ◽  
Anthony W. I. Lo ◽  
Cindy S. W. Tong ◽  
Don W. C. Ching ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Cortex ◽  
Brain Injury
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