A novel mouse model for the study of endogenous neural stem and progenitor cells after traumatic brain injury

Anderson, Jeremy; Patel, Misaal; Forenzo, Dylan; Ai, Xin; Cai, Chaoxian; Wade, Quinn; Risman, Rebecca; Cai, Li

doi:10.1016/j.expneurol.2019.113119

Cited by 8 publications

(14 citation statements)

References 71 publications

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“…In these studies, the Cai lab has demonstrated that GFP+ NSPCs preferentially differentiate into interneurons of the brain and spinal cord during embryonic development and in adulthood [43,67]. Injury increased the number of GFP+ NSPCs and interneurons at the injury site in a closed head injury model [67]. These results demonstrate that the endogenous NSPCs in the brain proliferate after injury and differentiate into specific cell fates (Figure 3B).…”

Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 85%

“…The canonical Notch signaling pathway is required to regulate the quiescence, proliferation, and differentiation of NSPCs in the CNS [43,[65][66][67]. The Cai lab identified a 399bp cis-element in the second intron of the Notch1 locus (CR2) [68].…”

Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 99%

“…The cell fate of GFP tagged interneuron progenitors have been characterized in both normal development and neurological disease/injury conditions, which facilitate the study of the potentials of NSPCs in regenerative medicine [43,66,68]. In these studies, the Cai lab has demonstrated that GFP+ NSPCs preferentially differentiate into interneurons of the brain and spinal cord during embryonic development and in adulthood [43,67]. Injury increased the number of GFP+ NSPCs and interneurons at the injury site in a closed head injury model [67].…”

Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 99%

“…The stem cell behavior of these populations has been implicated in the injury response and neurodegenerative/demyelinating disorders [71]. These populations are primarily glial producing cells; however, extrinsic and intrinsic factors have been used to modulate the glial fate to neuronal fate for functional recovery after traumatic injury [46,67]. Both populations have also been polemically associated with the glial scar formation after TBI and SCI in mammals [72,73].…”

Section: Controversial Nspc Populations In Injury/diseasementioning

confidence: 99%

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Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Finkel

Esteban

Rodriguez

et al. 2021

Preprint

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Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

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Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 85%

Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 99%

Section: Notch1cr2-gfp+ Nspcs In Development and Injurymentioning

confidence: 99%

Section: Controversial Nspc Populations In Injury/diseasementioning

confidence: 99%

See 2 more Smart Citations

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Finkel

Esteban

Rodriguez

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…With no effective restorative therapies currently available, 2,3 interest has turned toward neural stem cells (NSCs)/progenitor cells, as they can dynamically sense the injured microenvironment, and can respond with a multitude of restorative factors that alter the injury milieu. Targeting the endogenous NSCs by altering them to modify the injury milieu 4 may improve the outcome after TBI. Therefore, understanding the NSC response to TBI has the potential to identify new therapeutic strategies for the treatment of TBI.…”

Section: Introductionmentioning

confidence: 99%

Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

Pringle

Solomon

Coles

et al. 2021

Neurotrauma Reports

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Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2'-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.

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Elucidation of Regional Mechanical Properties of Brain Tissues Based on Cell Density

2021

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Research on the mechanical properties of brain tissue has received extensive attention. However, most of the current studies have been conducted at the phenomenological level. In this study, the indentation method was used to explore the difference in local mechanical properties among different regions of the porcine cerebral cortex. Further, hematoxylin-eosin and immunofluorescence staining methods were used to determine the correlation between the cellular density at different test points and mechanical properties of the porcine cerebral cortex. The frontal lobe exhibited the strongest viscosity. The temporal lobe displayed the lowest sensitivity to changes in the indentation speed, and the occipital lobe exhibited the highest shear modulus. Additionally, the shear modulus of different areas of the cerebral cortex was negatively correlated with the total number of local cells per unit area and positively correlated with the number of neuronal cell bodies per unit area. Exploration of the mechanical properties of the local brain tissue can provide basic data for the establishment of a finite element model of the brain and mechanical referential information for the implantation position of brain chips.

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A novel mouse model for the study of endogenous neural stem and progenitor cells after traumatic brain injury

Cited by 8 publications

References 71 publications

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

Elucidation of Regional Mechanical Properties of Brain Tissues Based on Cell Density

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