Transplantation of <b><i>N</i></b>-Acetyl Aspartyl-Glutamate Synthetase-Activated Neural Stem Cells after Experimental Traumatic Brain Injury Significantly Improves Neurological Recovery

Abstract

Background/Aims: Neural stem cells (NSCs) hold considerable potential as a therapeutic tool for repair of the damaged nervous system. In the current study, we examined whether transplanted N-acetyl aspartyl-glutamate synthetase (NAAGS)-activated NSCs (NAAGS/NSCs) further improve neurological recovery following traumatic brain injury (TBI) in Sprague-Dawley rats. Methods: Animals received TBI and stereotactic injection of NSCs, NAAGS/NSCs or phosphate buffered saline without cells (control) into the injured cortex. NAAGS protein expression was detected through western blot analysis. Dialysate NAAG levels were analyzed with radioimmunoassay. Cell apoptosis was detected via TUNEL staining. The expression levels of specific pro-inflammatory cytokines were detected with enzyme-linked immunosorbent assay. Results: Groups with transplanted NSCs and NAAGS/NSCs displayed significant recovery of the motor behavior, compared to the control group. At 14 and 21 days post-transplantation, the motor behavior in NAAGS/NSC group was significantly improved than that in NSC group (p<0.05). Additionally, transplanted NAAGS/NSCs inhibited cell apoptosis and the expression levels of specific pro-inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α. Conclusion: Our results collectively demonstrate that NAAGS/NSCs provide a more powerful autoplastic therapy for the injured nervous system.

Neural stem/progenitor cells differentiate into oligodendrocytes, reduce inflammation, and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury

“…Our results on rescue of mechanical injury‐related cognitive deficits are in line with previous studies showing that transplantation of NPCs isolated from various sources such as rat (Blaya et al, ) or human embryos (Gao et al, ) as well as immortalized cell lines from the early postnatal mouse cerebellum (Bakshi et al, ) have the potential to ameliorate cognitive decline caused by TBI. In conjunction with other reports indicating the potential of NPCs to ameliorate motor deficits induced by TBI (Li et al, ; Ma et al, ; Shear et al, ; Wang et al, ) or spinal cord injury (Hwang et al, ; Yan et al, ; Yasuda et al, ), our data suggest that NPCs would be useful as putative therapeutic agents for CNS trauma provided they can sustain a long‐term functional outcome (Makri et al, ; Skardelly et al, ). In our model early postnatal NPC grafts have lost their proliferative capacity by the second month after transplantation, indicating minimal risk of tumorigenesis if used as a potential therapeutic means in brain injuries.…”

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

“…Apoptosis-induced DNA fragmentation was determined using the transferase mediated deoxyuridine triphosphate(dUTP)-digoxigenin nick-end labeling (TUNEL) assay [24]. The astrocytes from different groups were fixed with 4% (w/v) paraformaldehyde and processed by using a commercial kit (Roche) in accordance with the manufacturer's instructions.…”

Silencing of A20 Aggravates Neuronal Death and Inflammation After Traumatic Brain Injury: A Potential Trigger of Necroptosis

“…During this phase, a variety of types of programmed cell death lead to neuronal loss (Dusick et al, 2012; Hinson et al, 2015). These events are sometimes accompanied by cognitive and neurological deficits in human TBI and in rat models of experimentally controlled cortical impact (CCI) injury (Li et al, 2013; Muccigrosso et al, 2016). During therapy, the pathway affected by the initial mechanical tissue disruption is refractory to treatment.…”