Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post—Traumatic brain injury

Ghazale, Hussein; Ramadan, Naify; Mantash, Sarah; Zibara, Kazem; El-Sitt, Sally; Darwish, Hala; Chamaa, Farah; Boustany, Rose Mary; Mondello, Stefania; Abou-Kheir, Wassim; Soueid, Jihane; Kobeissy, Firas

doi:10.1016/j.bbr.2017.11.007

Cited by 26 publications

(14 citation statements)

References 109 publications

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“…These neuropathological sequelae happen progressively, aggravating the neural injury and inducing neuropsychological and motor deficits. Thus, several options have been proposed as a prospective therapy for TBI including stem cell transplantation using mesenchymal stem cells (MSCs) ( 26 , 48 ), neural stem cells (NSCs) ( 27 – 30 ), induced pluripotent stem cells (iPSCs) ( 31 ) and embryonic neural stem cells (ENSCs) ( 32 ). Thus, the aim of our study was to investigate the effect of grafting different cell types (ENSCs or DCs) on neuroinflammation and neurogenesis after mild CCI.…”

Section: Discussionmentioning

confidence: 99%

“…The role of stem cells in tissue reconstruction, neuroprotection and trophic support to the host tissue makes them a potential therapeutic option ( 25 ). Recently, neural transplantation as a prospective therapy for TBI has emerged using mesenchymal stem cells (MSCs) ( 26 ), neural stem cells (NSCs) ( 27 – 30 ), induced pluripotent stem cells (iPSCs) ( 31 ) and embryonic neural stem cells (ENSCs) ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of Embryonic Neural Stem Cells and Differentiated Cells in a Controlled Cortical Impact (CCI) Model of Adult Mouse Somatosensory Cortex

et al. 2018

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Traumatic brain injury (TBI) is a major cause of death worldwide. Depending on the severity of the injury, TBI can reflect a broad range of consequences such as speech impairment, memory disturbances, and premature death. In this study, embryonic neural stem cells (ENSC) were isolated from E14 mouse embryos and cultured to produce neurospheres which were induced to generate differentiated cells (DC). As a cell replacement treatment option, we aimed to transplant ENSC or DC into the adult injured C57BL/6 mouse cortex controlled cortical impact (CCI) model, 7 days post-trauma, in comparison to saline injection (control). The effect of grafted cells on neuroinflammation and neurogenesis was investigated at 1 and 4 weeks post-transplantation. Results showed that microglia were activated following mild CCI, but not enhanced after engraftment of ENSC or DC. Indeed, ipsilateral lesioned somatosensory area expressed high levels of Iba-1+ microglia within the different groups after 1 and 4 weeks. On the other hand, treatment with ENSC or DC demonstrated a significant reduction in astrogliosis. The levels of GFAP expressing astrocytes started decreasing early (1 week) in the ENSC group and then were similarly low at 4 weeks in both ENSC and DC. Moreover, neurogenesis was significantly enhanced in ENSC and DC groups. Indeed, a significant increase in the number of DCX expressing progenitor cells was observed at 1 week in the ENSC group, and in DC and ENSC groups at 4 weeks. Furthermore, the number of mature neuronal cells (NeuN+) significantly increased in DC group at 4 weeks whereas they decreased in ENSC group at 1 week. Therefore, injection of ENSC or DC post-CCI caused decreased astrogliosis and suggested an increased neurogenesis via inducing neural progenitor proliferation and expression rather than neuronal maturation. Thus, ENSC may play a role in replacing lost cells and brain repair following TBI by improving neurogenesis and reducing neuroinflammation, reflecting an optimal environment for transplanted and newly born cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transplantation of Embryonic Neural Stem Cells and Differentiated Cells in a Controlled Cortical Impact (CCI) Model of Adult Mouse Somatosensory Cortex

et al. 2018

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“…The same group also investigated the therapeutic window following focal hypoxiaischemia in rats and found a single dose of 5 mg/kg DHA to be significantly effective up to 5 hours post insult 139 . In a model of traumatic brain injury (TBI), DHA has been administered together with neonatal neural stem cells (NSC) into the brain injured mouse, and results show that pretreatment with DHA may be a desirable strategy to improve the therapeutic efficacy of NSC transplantation in TBI 140 . There are some studies on DHA dietary supplementation in infants and children with and without neurological disability 141,142 .…”

Section: Therapeutic Use In Experimental Neonatology and Pediatricsmentioning

confidence: 99%

DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

Huun

Garberg

Escobar

et al. 2018

Journal of Perinatal Medicine

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“…Treated animals also demonstrated decreases in both GFAP fragmentation and αII-spectrin proteolysis, both of which have recently been validated as potential biomarkers of necrotic calpain-mediated neural injury. This suggests a downregulation of calpain/caspase activation (Ghazale et al, 2018).…”

Section: Traumatic Brain Injurymentioning

confidence: 94%

“…Docosahexaenoic acid (DHA) is a common polyunsaturated structural lipid in the brain which furthers brain development via neuron differentiation, neurite enlargement, and formation of synapses (Tanaka et al, 2012). Pup mice-derived NSCs pre-treated with DHA mitigated TBI-induced motor deficits, enhanced neurogenesis, and elevated glial reactivity when transplanted at the site of injury in a murine TBI model (Ghazale et al, 2018). Treated animals also demonstrated decreases in both GFAP fragmentation and αII-spectrin proteolysis, both of which have recently been validated as potential biomarkers of necrotic calpain-mediated neural injury.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Stem cell therapy for neurological disorders: A focus on aging

Nguyen

Zarriello

Coats

et al. 2019

Neurobiology of Disease

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Age-related neurological disorders continue to pose a significant societal and economic burden. Aging is a complex phenomenon that affects many aspects of the human body. Specifically, aging can have detrimental effects on the progression of brain diseases and endogenous stem cells. Stem cell therapies possess promising potential to mitigate the neurological symptoms of such diseases. However, aging presents a major obstacle for maximum efficacy of these treatments. In this review, we discuss current preclinical and clinical literature to highlight the interactions between aging, stem cell therapy, and the progression of major neurological disease states such as Parkinson's disease, Huntington's disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis, and multiple system atrophy. We raise important questions to guide future research and advance novel treatment options.

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Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post—Traumatic brain injury

Cited by 26 publications

References 109 publications

Transplantation of Embryonic Neural Stem Cells and Differentiated Cells in a Controlled Cortical Impact (CCI) Model of Adult Mouse Somatosensory Cortex

Transplantation of Embryonic Neural Stem Cells and Differentiated Cells in a Controlled Cortical Impact (CCI) Model of Adult Mouse Somatosensory Cortex

DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

Stem cell therapy for neurological disorders: A focus on aging

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