In vitro P38MAPK inhibition in aged astrocytes decreases reactive astrocytes, inflammation and increases nutritive capacity after oxygen-glucose deprivation

Abstract

Proper astroglial functioning is essential for the development and survival of neurons and oligodendroglia under physiologic and pathological circumstances. Indeed, malfunctioning of astrocytes represents an important factor contributing to brain injury. However, the molecular pathways of this astroglial dysfunction are poorly defined. In this work we show that aging itself can drastically perturb astrocyte viability with an increase of inflammation, cell death and astrogliosis. Moreover, we demonstrate that oxygen glucose deprivation (OGD) has a higher impact on nutritive loss in aged astrocytes compared to young ones, whereas aged astrocytes have a higher activity of the anti-oxidant systems. P38MAPK signaling has been identified to be upregulated in neurons, astrocytes and microglia after ischemic stroke. By using a pharmacological p38α specific inhibitor (PH-797804), we show that p38MAPK pathway has an important role in aged astrocytes for inflammatory and oxidative stress responses with the subsequent cell death that occurs after OGD.

Oleuropein Inhibits Astrocyte Damage Induced by Oxygen-Glucose Deprivation

“…The main factors causing ischemic stroke include oxidative damage, apoptosis, autophagy, inflammation, energy metabolism disorders, and so on [23] . Cellular defense in the brain involves endogenous protective enzymes, such as SOD, which are produced by astrocytes to protect neurons from oxidative stress [24] . In addition, oxidative stress markers in induction of apoptosis and autophagy [29] .…”

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation

“…miR-128-3p has been found to mitigate penicillin-induced apoptosis and restrict inflammation in astrocytes implicated in epilepsy by modulating the MAPK6 pathway [ 50 ]. Inhibiting P38MAPK has been shown to attenuate the response of astrocytes, resulting in decreased inflammation in aged astrocytes [ 51 ]. Similarly, miR-499a targeting PTEN in astrocytes has demonstrated comparable anti-inflammatory effects in the context of ischemic stroke [ 52 ].…”

Pre exposure to enriched environment alleviates brain injury after ischemia-reperfusion by inhibiting p38MAPK/STAT1 pathway

“…An increasing body of evidence suggests that that p38MAPK/STAT1 pathway plays a significant role in the inflammatory response [23]. p38MAPK signaling pathway is also participated in the pathological process of stroke, which has been validated in numerous cellular and animal experiments [24][25][26][27]. However, it is not clear whether the p38MAPK/STAT1 pathway is associated with the protective effect of EE pretreatment.…”