FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage

Okada, Takeshi; Enkhjargal, Budbazar; Travis, Zachary D.; Ocak, Umut; Tang, Jiping; Suzuki, Hitomi; Zhang, Junyi

doi:10.1007/s12035-019-01668-9

Cited by 56 publications

(57 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( 90 ) found significantly increased FGF2 mRNA transcripts and protein levels associated to white matter astrocytes in the initial phase of remyelination, indicating that astrocyte-derived FGF2 may modulate the differentiation of oligodendrocytes ( 206 ) ( Figure 2 ) . Other potential effects of astrocyte-derived FGF2 include the attenuation of neuronal death via signaling through FGFR3 ( 207 ) and autocrine/paracrine regulation of glia reactivity ( 199 ). The therapeutic potential of FGF2 is recapitulated in a comprehensive study by Ruffini et al.…”

Section: Protective Effects Of Reactive Astrocytes Following Cns Insumentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

View full text Add to dashboard Cite

Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer's disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.

show abstract

Section: Protective Effects Of Reactive Astrocytes Following Cns Insumentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

View full text Add to dashboard Cite

show abstract

“…Therefore, the influence of APC366 on the inhibition of other proteases cannot be ignored while considering its reported in vivo effects on MCtryptase. Nevertheless, we elected to proceed with APC366 to inhibit tryptase rather than more specific inhibitors such as specific tryptase silencing RNA (siRNA) or tryptase CRISPR (clustered regularly interspaced short palindromic repeats) knockout plasmids due to the following reasons: (1) intraventricular injection at 24-48 h prior to injury induction is a common route to deliver these specific siRNA or CRISPRs to the brain in rodent models of neurological diseases [22,25,29,35,70,71], which could have further decreased the almost 70% ROCS success of our model given the potential complications due to the intraventricular injection procedure.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats

Ocak

Huang

et al. 2020

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background: Cardiac arrest survivors suffer from neurological dysfunction including cognitive impairment. Cerebral mast cells, the key regulators of neuroinflammation contribute to neuroinflammation-associated cognitive dysfunction. Mast cell tryptase was demonstrated to have a proinflammatory effect on microglia via the activation of microglial protease-activated receptor-2 (PAR-2). This study investigated the potential anti-neuroinflammatory effect of mast cell tryptase inhibition and the underlying mechanism of PAR-2/p-p38/NFκB signaling following asphyxia-induced cardiac arrest in rats. Methods: Adult male Sprague-Dawley rats resuscitated from 10 min of asphyxia-induced cardiac arrest were randomized to four separate experiments including time-course, short-term outcomes, long-term outcomes and mechanism studies. The effect of mast cell tryptase inhibition on asphyxial cardiac arrest outcomes was examined after intranasal administration of selective mast cell tryptase inhibitor (APC366; 50 μg/rat or 150 μg/rat). AC55541 (selective PAR-2 activator; 30 μg/rat) and SB203580 (selective p38 inhibitor; 300 μg/rat) were used for intervention. Short-term neurocognitive functions were evaluated using the neurological deficit score, number of seizures, adhesive tape removal test, and T-maze test, while long-term cognitive functions were evaluated using the Morris water maze test. Hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining.

show abstract

“…An animal model study of the pathological process of SAH found that insulin-like growth factor-1 remarkably increased pAkt expression, and then reduced the percentage of apoptotic cells after SAH, indicating that insulin-like growth factor-1 played a protective role by activating the PI3K signalling pathway, and administration of Ly294002 (PI3K pathway inhibitor) notably induced the increase of apoptotic cells [16]. The Akt/ GSK3b signalling pathway plays a role in reducing brain nerve injury after SAH [17]. In the PI3K-AKT signalling pathway, MSR1 can inhibit the progress of chronic myelogenous leukaemia by regulating PI3K-AKT signalling pathway and b-catenin expression [18].…”

Section: Kegg Pathway Enrichment Analysismentioning

confidence: 99%

Gene expression profiles and related immune-inflammatory factors in the cerebral arteries in mouse models of subarachnoid haemorrhage

Wang

Han

Wang

et al. 2020

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

The study aimed to identify key genes involved in cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). GSE46696 of basilar arteries of SAH mice and normal controls were downloaded from the Gene Expression Omnibus (GEO). Integrated microarray analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses of DEGs were performed with ClueGO. The protein-protein interaction (PPI) networks were constructed using Cytoscape software. A total of 4103 DEGs were identified; among them, 254 DEGs (63 up-regulated genes and 191 down-regulated genes) showed significant differences at p < 0.05. GO analysis showed that the identified DEGs were over-represented in 16 GO terms. KEGG pathway analysis showed that pathways in immune inflammation were significantly enriched pathways for DEGs. DEGs with relatively frequent interactions after CVS secondary to SAH included MIKI,

show abstract

FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage

Cited by 56 publications

References 32 publications

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats

Gene expression profiles and related immune-inflammatory factors in the cerebral arteries in mouse models of subarachnoid haemorrhage

Contact Info

Product

Resources

About