Ultrastructural Characteristics of Neuronal Death and White Matter Injury in Mouse Brain Tissues After Intracerebral Hemorrhage: Coexistence of Ferroptosis, Autophagy, and Necrosis

Li, Qian; Weiland, Abigail; Chen, Xuemei; Lan, Xi; Han, Xiaoning; Durham, Frederick; Liu, Xi; Wan, Jieru; Ziai, Wendy; Hanley, Daniel F.; Wang, Jian

doi:10.3389/fneur.2018.00581

Cited by 130 publications

(107 citation statements)

References 63 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Zille et al (2017) also confirmed that ferroptosis and necroptosis were the main features of experimental hemorrhagic stroke in vitro and in vivo and suggested that the ferroptosis inhibitor deferoxamine may elicit significant functional recovery in some models and clinical patients of ICH. Li et al (2018) also observed the ultrastructure of ICH-induced pathology through transmission electron microscopy, including in cells undergoing ferroptosis, necroptosis, and autophagy.…”

Section: Intracerebral Hemorrhage and Ferroptosismentioning

confidence: 98%

The Potential Value of Targeting Ferroptosis in Early Brain Injury After Acute CNS Disease

Chen

Wang

et al. 2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Acute central nervous system (CNS) disease is very common and with high mortality. Many basic studies have confirmed the molecular mechanism of early brain injury (EBI) after acute CNS disease. Neuron death and dysfunction are important reasons for the neurological dysfunction in patients with acute CNS disease. Ferroptosis is a nonapoptotic form of cell death, the classical characteristic of which is based on the iron-dependent accumulation of toxic lipid reactive oxygen species. Previous studies have indicated that this mechanism is critical in the cell death events observed in many diseases, including cancer, tumor resistance, Alzheimer's disease, Parkinson's disease, stroke, and intracerebral hemorrhage (ICH). Ferroptosis may also play a very important role in EBI after acute CNS disease. Unresolved issues include the relationship between ferroptosis and other forms of cell death after acute CNS disease, the specific molecular mechanisms of EBI, the strategies to activate or inhibit ferroptosis to achieve desirable attenuation of EBI, and the need to find new molecular markers of ferroptosis that can be used to detect and study this process in vivo after acute CNS disease.

show abstract

Section: Intracerebral Hemorrhage and Ferroptosismentioning

confidence: 98%

The Potential Value of Targeting Ferroptosis in Early Brain Injury After Acute CNS Disease

Chen

Wang

et al. 2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Morphologically, the mitochondria of ferroptotic neurons appeared shrunken, with decreased cytomembrane mitochondria at 3 and 6 days after ICH in mice. After several days, the swollen mitochondrial count appears to stabilize and is sustained until 28 days (Li et al, 2018). Interestingly, another study failed to find the shrunken mitochondria in primary neurons subjected to hemin stimulation (Zille et al, 2017).…”

Section: Ferroptosis In Hemorrhagic Strokementioning

confidence: 99%

Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke

Fang

Gao

Wang

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Hemorrhagic stroke is a life-threatening neurological disease characterized by high mortality and morbidity. Various pathophysiological responses are initiated after blood enters the interstitial space of the brain, compressing the brain tissue and thus causing cell death. Recently, three new programmed cell deaths (PCDs), necroptosis, pyroptosis, and ferroptosis, were also found to be important contributors in the pathophysiology of hemorrhagic stroke. Additionally, blood-brain barrier (BBB) dysfunction plays a crucial role in the pathophysiology of hemorrhagic stroke. The primary insult following BBB dysfunction may disrupt the tight junctions (TJs), transporters, transcytosis, and leukocyte adhesion molecule expression, which may lead to brain edema, ionic homeostasis disruption, altered signaling, and immune infiltration, consequently causing neuronal cell death. This review article summarizes recent advances in our knowledge of the mechanisms regarding these new PCDs and reviews their contributions in hemorrhagic stroke and potential crosstalk in BBB dysfunction. Numerous studies revealed that necroptosis, pyroptosis, and ferroptosis participate in cell death after subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). Endothelial dysfunction caused by these three PCDs may be the critical factor during BBB damage. Also, several signaling pathways were involved in PCDs and BBB dysfunction. These new PCDs (necroptosis, pyroptosis, ferroptosis), as well as BBB dysfunction, each play a critical role after hemorrhagic stroke. A better understanding of the interrelationship among them might provide us with better therapeutic targets for the treatment of hemorrhagic stroke.

show abstract

“…Fragmentation and degeneration of organelles exposes more proteins or polypeptides, which contain amino groups to which osmic acid can easily adsorb, resulting in electron density under an electron microscope. According to the current literature [21,51,54], degeneration of neuronal cytoplasm and synaptic boutons is characterized by dark electron density under an electron microscope.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the NMJ boutons contained autophagosomes (Fig. 6H-H') [54] and abnormal mitochondria (Fig. 8E, E''), which are associated with synaptic degeneration [13].…”

Section: Discussionmentioning

confidence: 99%

Neurexin and Neuroligins Jointly Regulate Synaptic Degeneration at the Drosophila Neuromuscular Junction based on TEM Studies

G¹,

Chenchen²,

Xiang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development and signal transmission in neurology. Here, we show the synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies.Methods: To this aim, we extensively acquire the ultrastructure of diffuse NMJ boutons using continuous sectioning and transmission electron microscope in the wide type and the dneurexin (dnrx) and dneuroligins (dngs) mutant.Results: When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and then, the residual SSR degenerates into a disordered, thin or linear membrane with a shrinking postsynaptic area (PSA) and axon terminal. The axon terminal begins to degenerate from the central region, and the T-bar structure detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration, accompanied by retraction of synaptic vesicles and mitochondria. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons, including presynaptic and postsynaptic membranes, become very thin, most of the SSR degenerates into a linear shape, and all the residual elements in axon terminals, such as synaptic vesicles, mitochondria, the cytoskeleton, and the T-bar, degenerate in situ and eventually form a cluster of dark ultrafine particles. Axon terminals and elements within axon terminals degenerate with the postsynaptic SSR, and swelling and retraction of the SSR occurs prior to axon terminal degradation, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions, but degeneration in dnrx and dnlgs mutant is accelerated. Furthermore, there is a synergistic effect in dnrx;dnlgs double mutants and dnlg2;dnlg3 double mutants that promotes degeneration of NMJ boutons.Conclusions: NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in dnrx and dnlgs mutants. Furthermore, there is a synergistic effect in dnrx;dnlgs double mutants and dnlg2;dnlg3 double mutants that promotes degeneration of NMJ boutons, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration. This study proposes the model of NMJ bouton degeneration patterns, which is very conducive to in-depth study of neurodegeneration.

show abstract

Ultrastructural Characteristics of Neuronal Death and White Matter Injury in Mouse Brain Tissues After Intracerebral Hemorrhage: Coexistence of Ferroptosis, Autophagy, and Necrosis

Cited by 130 publications

References 63 publications

The Potential Value of Targeting Ferroptosis in Early Brain Injury After Acute CNS Disease

The Potential Value of Targeting Ferroptosis in Early Brain Injury After Acute CNS Disease

Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke

Neurexin and Neuroligins Jointly Regulate Synaptic Degeneration at the Drosophila Neuromuscular Junction based on TEM Studies

Contact Info

Product

Resources

About