Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive im...Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
Objective: to identify the socio-demographic profile of the alleged victims of sexual assault, to define the characteristics of the aggressors, to describe the types of clinical lesions, and to analyze the link betwee...Objective: to identify the socio-demographic profile of the alleged victims of sexual assault, to define the characteristics of the aggressors, to describe the types of clinical lesions, and to analyze the link between these different parameters.?During the study period, 5620 clients were admitted to gynecological emergencies, including 150 for sexual assault (2.6%). The alleged victims of aggression were 14 years old on average [range: 2?-?49 years]. Among these clients, there were 147 (98%) women and 3 (2%) men [sex ratio: 0.02]. They had a primary education level of 38%, secondary to 42.7%, and single in 87.2% of cases. Clients came from home (69.3%) or police station (24.7%). The perpetrator was male, with an average age of 25.5 years [range: 16 to 35 years]. Regarding the relationship with the victim, the neighborhood accounted for 83%. The perpetrator was alone in 76.7% of cases, two (14%) or more (16.7%), up to 18.?The aggressor’s home was the place of aggression (39.3%). The threats were made using knives (49.3%) and firearms (8.5%). The perpetrator used either his sex (79.9%), his fingers (34.2%) or an object (2.7%). The route of entry was vaginal (94.6%), anal (21.7%) and oral (10%). The abuser used the condom in 74.7% of cases.?Customers had viewed within 24 hours (40.7%). The general state and hemodynamics at admission was normal for all clients. Physical injuries were injuries (23%) and scrapes (34.5%). External genitalia included perineal tears (28%), vaginal tears (8.6%), hymenal tears (7.3%), and old deflowering (72.7%). The hymen was intact in 20%.?The bi-varied analysis found a correlation with a statistically significant difference in the age range of the alleged victims with the number of aggressors, the time of aggression, the path and type of penetration, and the weapon used for the threat.展开更多
基金supported by grants PICT 2019-08512017-2203,UBACYT and PIP CONICET(to AJR).
文摘Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
文摘Objective: to identify the socio-demographic profile of the alleged victims of sexual assault, to define the characteristics of the aggressors, to describe the types of clinical lesions, and to analyze the link between these different parameters.?During the study period, 5620 clients were admitted to gynecological emergencies, including 150 for sexual assault (2.6%). The alleged victims of aggression were 14 years old on average [range: 2?-?49 years]. Among these clients, there were 147 (98%) women and 3 (2%) men [sex ratio: 0.02]. They had a primary education level of 38%, secondary to 42.7%, and single in 87.2% of cases. Clients came from home (69.3%) or police station (24.7%). The perpetrator was male, with an average age of 25.5 years [range: 16 to 35 years]. Regarding the relationship with the victim, the neighborhood accounted for 83%. The perpetrator was alone in 76.7% of cases, two (14%) or more (16.7%), up to 18.?The aggressor’s home was the place of aggression (39.3%). The threats were made using knives (49.3%) and firearms (8.5%). The perpetrator used either his sex (79.9%), his fingers (34.2%) or an object (2.7%). The route of entry was vaginal (94.6%), anal (21.7%) and oral (10%). The abuser used the condom in 74.7% of cases.?Customers had viewed within 24 hours (40.7%). The general state and hemodynamics at admission was normal for all clients. Physical injuries were injuries (23%) and scrapes (34.5%). External genitalia included perineal tears (28%), vaginal tears (8.6%), hymenal tears (7.3%), and old deflowering (72.7%). The hymen was intact in 20%.?The bi-varied analysis found a correlation with a statistically significant difference in the age range of the alleged victims with the number of aggressors, the time of aggression, the path and type of penetration, and the weapon used for the threat.
