Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte

Abstract

Mesenchymal stem cell (MSC) transplantation reduces the neurological impairment caused by hypoxic-ischemic brain damage (HIBD) via immunomodulation. In the current study, we found that MSC transplantation improved learning and memory function and enhanced long-term potentiation in neonatal rats subjected to HIBD and the amount of IL-6 released from MSCs was far greater than that of other cytokines. However, the neuroprotective effect of MSCs infected with siIL-6-transduced recombinant lentivirus (siIL-6 MSCs) was significantly weakened in the behavioural tests and electrophysiological analysis. Meanwhile, the hippocampal IL-6 levels were decreased following siIL-6 MSC transplantation. In vitro, the levels of IL-6 release and the levels of IL-6R and STAT3 expression were increased in both primary neurons and astrocytes subjected to oxygen and glucose deprivation (OGD) following MSCs co-culture. The anti-apoptotic protein Bcl-2 was upregulated and the pro-apoptotic protein Bax was downregulated in OGD-injured astrocytes co-cultured with MSCs. However, the siIL-6 MSCs suppressed ratio of Bcl-2/Bax in the injured astrocytes and induced apoptosis number of the injured astrocytes. Taken together, these data suggest that the neuroprotective effect of MSC transplantation in neonatal HIBD rats is partly mediated by IL-6 to enhance anti-apoptosis of injured astrocytes via the IL-6/STAT3 signaling pathway.

Brain-immune interactions in perinatal hypoxic-ischemic brain injury

“…In human neonates with perinatal asphyxia, the levels of IL-6 are significantly higher and show a biphasic pattern with early and delayed peaks (Jenkins et al , 2012). IL-6 enhances anti-apoptotic activity of astrocytes through the IL-6/STAT3 signaling in neonatal rats with HI brain injury (Gu et al , 2016). Thus, it is possible that IL-6 protects neurons and glia from apoptotic cell death at a delayed phase in the immature brain, but a significant anti-inflammatory role of IL-6 after neonatal HI insult has not been fully elucidated yet.…”

Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats

“…A mechanism pertaining to the death of immature neurons is the accumulation of AIF and Cyt c, which is safely sequestered within the mitochondrial intermembrane space in non-apoptotic cells (Guo et al, 2002). On the other hand, anti-apoptotic protein Bcl-2, also known as a mitochondrial membrane protein, blocks the apoptotic death of many cell types (Deanna L. Taylor et al, 1999;Gu et al, 2016), it plays a crucial role in regulation of mitochondria-mediated cell death. Therefore, anti-apoptotic therapies via inhibiting AIF and Cyt c expression and modulating the actions of Bcl-2 family proteins have been proposed to be useful in ameliorating neonatal HIBD.…”

“…Neonatal hypoxic-ischemic brain damage (HIBD) is a relatively common malignant complication caused by clinical perinatal asphyxia in infants and young children (Chen et al, 2015;Thatipamula et al, 2015), which occurs in 1 to 6 of every 1,000 live term births (Gu et al, 2016;Koonrungsesomboon et al, 2014). Statistics suggests that approximately 40% of the affected infants die in the neonatal period and an additional 30% have lifelong neurological deficits including cerebral palsy, epilepsy and cognitive disabilities (Hristova et al, 2016).…”

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

“…As the cells reached 90% confluence, the medium was replaced with Earle balanced salt solution (PH1509, HyClone, USA). Subsequently, neuronal cells were cultured in an incubator containing 5% O 2 and 95% N 2 at 37 °C for 6 h. Normal neuronal cells did not undergo OGD model induction and were used as the control group [21-23]. …”