scholarly journals Enriching neural stem cell and pro-healing glial phenotypes with electrical stimulation after traumatic brain injury in male rats

2020 ◽  
Author(s):  
Eunyoung Park ◽  
Johnathan G. Lyon ◽  
Melissa Alvarado-Velez ◽  
Martha I. Betancur ◽  
Nassir Mokarram ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Electrical Stimulation ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Acute Phase ◽  
Immune Cells ◽  
Male Rats ◽  
Cell Phenotype ◽  
Injury Site

AbstractTraumatic Brain Injury (TBI) by an external physical impact results in compromised brain function via undesired neuronal death. Following the injury, resident and peripheral immune cells, astrocytes, and neural stem cells (NSCs) cooperatively contribute to the recovery of the neuronal function after TBI. However, excessive pro-inflammatory responses of immune cells, and the disappearance of endogenous NSCs at the injury site during the acute phase of TBI, can exacerbate TBI progression leading to incomplete healing. Therefore, positive outcomes may depend on early interventions to control the injury-associated cellular milieu in the early phase of injury. Here, we explore electrical stimulation (ES) of the injury site in a rodent model (male Sprague-Dawley rats) to investigate its overall effect on the constituent brain cell phenotype and composition during the acute phase of TBI. Our data showed that a brief ES for 1h on day 2 of TBI promoted pro-healing phenotypes of microglia as assessed by CD206 expression and increased the population of NSCs and Nestin+ astrocytes at 7 days post-TBI. Also, ES effectively increased the number of viable neurons when compared to the unstimulated control group. Given the salience of microglia and neural stem cells for healing after TBI, our results strongly support the potential benefit of the therapeutic use of ES during the acute phase of TBI to regulate neuroinflammation and to enhance neuroregeneration.Significance StatementTraumatic brain injury (TBI) occurs when a head injury leads to a disruption of normal function in the brain and is a major cause of death and disability, worldwide. The authors used electrical stimulation during the acute phase of TBI, which promoted pro-healing phenotypes of microglia and increased the number of neural stem cells and Nestin+ astrocytes, thereby enhancing neuronal viability. These findings support further study of electrical stimulation to regulate neuroinflammation and to enhance neuroregeneration after TBI.Graphical AbstractFIGURE 1.

scholarly journals Enriching neural stem cell and anti‐inflammatory glial phenotypes with electrical stimulation after traumatic brain injury in male rats

2021 ◽  
Author(s):  
Eunyoung Park ◽  
Johnathan G. Lyon ◽  
Melissa Alvarado‐Velez ◽  
Martha I. Betancur ◽  
Nassir Mokarram ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cell ◽  
Electrical Stimulation ◽  
Brain Injury ◽  
Neural Stem Cell ◽  
Male Rats ◽  
Anti Inflammatory

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.

Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury

2006 ◽  
Vol 201 (2) ◽  
pp. 281-292 ◽  
Author(s):  
J GAO ◽  
D PROUGH ◽  
D MCADOO ◽  
J GRADY ◽  
M PARSLEY ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Cognitive Function ◽  
Neural Stem Cells

Activation of endogenous neural stem cells after traumatic brain injury

The Lancet ◽  
2014 ◽  
Vol 383 ◽  
pp. S18 ◽  
Author(s):  
Aminul Ahmed ◽  
Anan Shtaya ◽  
Malik Zaben ◽  
William Gray
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Endogenous Neural Stem Cells

Stem Cell Studies in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 373-386
Author(s):  
Dong Sun
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Stem Cell ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Survival Rates ◽  
Structural Repair ◽  
Potential Strategy ◽  
Endogenous Neural Stem Cells

Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rates after TBI, there is no effective treatment to improve the neural structural repair and functional recovery of patients. Neural regeneration through neural stem cells, either by stimulating endogenous neural stem cells or by stem cell transplantation, has gained increasing attention as a potential strategy to repair and regenerate the injured brain. This chapter summarizes strategies that have been explored to enhance endogenous neural stem cells-mediated regeneration and recent developments in cell transplantation studies for post-TBI brain repair with varying types of cell sources.

scholarly journals Efficacy of Minocycline in Neural Stem Cells Proliferation after Traumatic Brain Injury

2020 ◽  
Vol 8 (A) ◽  
pp. 59-64
Author(s):  
R. R. Suzy Indharty ◽  
Iskandar Japardi ◽  
Andre M. P. Siahaan ◽  
Steven Tandean ◽  
Michael Lumintang Loe
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Inflammatory Responses ◽  
Closed Head Injury ◽  
Related Factor ◽  
Sprague Dawley ◽  
Proliferation Capacity ◽  
Cell Counts

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that contributes to neurological impairments after traumatic brain injury (TBI). There is a robust evidence that neuroinflammation will diminish neurogenesis after TBI. Therefore, strategies to attenuate the inflammatory responses are potential to increase neurogenesis following TBI. Minocycline, a second-generation tetracycline antibiotic derivate, has potent anti-inflammatory effect by reducing microglial activation and suppressing some pro-inflammatory cytokines. AIM: The aim of this study is to investigate if minocycline could enhance neurogenesis after TBI. METHODS: Thirty Sprague Dawley rats were randomized into three treatments group, i.e., sham-operated controls, closed head injury (CHI), and CHI with minocycline. We used the modified Feeney’s weight-drop model for making CHI. For the treatment group, we gave minocycline per oral (50 mg/kg) twice daily for the first 2 days followed by 25 mg/kg once daily for 3 consecutive days. Animals were sacrificed on day 5. To assess the proliferation capacity of neural stem cells (NSC), we performed immunohistochemistry staining with SOX2, brain-derived neurotropic factor (BDNF), and NFR. Cell counts were carried out using light microscope with 1000 times magnification in 20 high-power fields. RESULTS: SOX2, NF-E2-related factor 2 (NRF-2), and BDNF were upregulated in the CHI group compared to the sham-operated group (p < 0.05). NRF-2, BDNF, and SOX2 were upregulated also significantly in the CHI+ minocycline group compared to the sham-operated group and the CHI group (p < 0.05). CONCLUSION: Minocycline increased the proliferation capacity of NSC.

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