The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have benefi...The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.展开更多
Necroptosis has been reported in the last years as a type of regulated cell death that can be ignited by a number of specific death receptors,such as FAS,tumor necrosis factor receptor 1(TNFR1),or pathogen recognition...Necroptosis has been reported in the last years as a type of regulated cell death that can be ignited by a number of specific death receptors,such as FAS,tumor necrosis factor receptor 1(TNFR1),or pathogen recognition receptors.This cell death subroutine is involved in the response to stress and in homeostatic functions,such as the maintenance of adult T-cell balance(Galluzzi et al.,2018).Dead receptor activation leads to the recruitment of protein complexes that act as nodes of signaling that can elicit different pathways driving to death or survival,depending on the cell conditions.展开更多
This perspective shows an attempt to obtain synergy effects to fight ischemic stroke by combining agents acting on two different homeostatic mechanisms:inflammation and unfolded protein response (Anuncibay-Soto et al....This perspective shows an attempt to obtain synergy effects to fight ischemic stroke by combining agents acting on two different homeostatic mechanisms:inflammation and unfolded protein response (Anuncibay-Soto et al.,2018).Different pharmacological approaches have been assayed to alleviate cerebrovascular accident (stroke), which represents one of the most devastating diseases in the elderly.展开更多
基金supported by MINECO and FEDER funds:ref CPP2021-008855 and RTC-2015-4094-1,Junta de Castilla y León ref.LE025P1 7Neural Therapies SLref.NTDev-01 (all to AFL and JMGO)。
文摘The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.
基金supported by MINECO and FEDER funds(RTC-2015-4094-1)+1 种基金by Junta de Castilla y León(LE025P17)by Neural therapies SL(NT-Dev-01).Paloma González-Rodríguez is granted from Junta de Castilla y León(EDU/529/2017).Enrique Font-Belmonte is supported by a grant from the University of León
文摘Necroptosis has been reported in the last years as a type of regulated cell death that can be ignited by a number of specific death receptors,such as FAS,tumor necrosis factor receptor 1(TNFR1),or pathogen recognition receptors.This cell death subroutine is involved in the response to stress and in homeostatic functions,such as the maintenance of adult T-cell balance(Galluzzi et al.,2018).Dead receptor activation leads to the recruitment of protein complexes that act as nodes of signaling that can elicit different pathways driving to death or survival,depending on the cell conditions.
基金This work was supported by the Spanish Ministerio de Economia y Competitividad(MINECO)co-financed with FEDER funds ‘‘una manera de hacer Europa"(reference RTC-2015-4094-1)+1 种基金Junta de Castilla y León(reference LE025P17)Neural Therapies SL(reference NT-Dev01)
文摘This perspective shows an attempt to obtain synergy effects to fight ischemic stroke by combining agents acting on two different homeostatic mechanisms:inflammation and unfolded protein response (Anuncibay-Soto et al.,2018).Different pharmacological approaches have been assayed to alleviate cerebrovascular accident (stroke), which represents one of the most devastating diseases in the elderly.
