GDF11 alleviates secondary brain injury after intracerebral hemorrhage via attenuating mitochondrial dynamic abnormality and dysfunction

Abstract

Intracerebral hemorrhage (ICH) is a serious public health problem with high rates of death and disability. The neuroprotective effect of Growth Differentiation Factor 11 (GDF11) in ICH has been initially proved by our previous study. Oxidative stress (OS) plays crucial roles in mediating subsequent damage of ICH. However, whether and how mitochondrial dynamic events and function participated in ICH pathophysiology, and how mitochondrial function and OS interreacted in the neuroprotective process of GDF11 in ICH remains unclarified. Based on the rat model of ICH and in vitro cell model, we demonstrated that GDF11 could alleviate ICH induced neurological deficits, brain edema, OS status, neuronal apoptosis and inflammatory reaction. In addition, mitochondrial functional and structural impairments were obviously restored by GDF11. Treatment with antioxidant protected against erythrocyte homogenate (EH) induced cell injury by restoring OS status and mitochondrial fusion fission imbalance, which was similar to the effect of GDF11 treatment. Further, inhibition of mitochondrial division with Mdivi-1 attenuated mitochondrial functional defects and neuronal damages. In conclusion, our results for the first time proposed that GDF11 protected the post-ICH secondary injury by suppressing the feedback loop between mitochondrial ROS production and mitochondrial dynamic alteration, resulting in attenuated mitochondrial function and amelioration of neural damage.

Mitochondrial Inhibitor Rotenone Triggers and Enhances Neuronal Ferroptosis Following Intracerebral Hemorrhage

“…Further validation experiments verified that ICH indeed causes mitochondrial damage in both humans and mice. Consistent with our data, other studies have also shown that ICH could markedly induce mitochondrial dysfunction in cells or animal ICH models. − Notably, we further found that damaged mitochondria presented ferroptosis-like morphological characteristics, indicating that mitochondria may be closely involved in ferroptosis after ICH.…”

Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration

“…[ 50 ] Mitotracker Red staining was used to visualize ultrastructure for quantifying mitochondrial length, volume, and network appearance. [ 51 ] Morphologically, mitochondria in the PEEK and SPEEK groups are shorter, rounder, and fragmented with less mitochondrial network continuity, which is reversed in the Zn&Sr‐SPEEK group with rod‐like and elongated mitochondria ( Figure 4 A ). Then, we carried out 3D reconstruction of mitochondria and quantified mitochondrial morphology and network appearance.…”

Extraction and purification of oridonin from Rabdosia rubescens and its protective effect on intracerebral hemorrhage-induced brain injury in rats

“…It plays an important role in the prognosis of ICH patients (Nakamura et al, 2010). The brain edema and neurological dysfunction are the main manifestations of ICH-induced brain injury (Xiao et al, 2021). In this study, the oridonin with purity of 97.42% was extracted and purified from Rabdosia rubescens.…”