Gas explosion injury is a compound injury caused by a shock wave,high-temperature flame,or toxic gas directly or indirectly acting on the human body,resulting in multiple organ damage.As a hyperaerated tissue,the lung...Gas explosion injury is a compound injury caused by a shock wave,high-temperature flame,or toxic gas directly or indirectly acting on the human body,resulting in multiple organ damage.As a hyperaerated tissue,the lung is the primary organ that experiences an early injury.The pathological manifestations of gas-explosion-induced acute lung injury(ALI)include pulmonary tissue edema.展开更多
Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional loss.Strong evidence ...Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional loss.Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2(ALDH2),a key oxidoreductase and powerful endogenous anti-aldehyde machinery,is likely important for protecting neurons from aldehydesmediated degeneration.Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator(Alda-1),we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2.Over an acute 2 day period post injury,we found that ALDH2 expression was significantly lowered post-SCI,but not so in rats given Alda-1.This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction,which was revealed in co-immunoprecipitation experiments.We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord,and reduced cyst pathology.In addition,Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI.Finally,ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure.It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims.All animal work was approved by Purdue Animal Care and Use Committee(approval No.1111000095)on January 1,2021.展开更多
Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously...Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat model.As such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral benefits.Methods:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats.The acrolein levels and related pathologies were measured by immunohistochemistry.Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test.Pain was assessed using mechanical allodynia,cold hypersensitivity,and plantar tests.Finally,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.Results:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and cortex.DP also mitigated both motor and sensory deficits typical of PD.In addition,DP lowered acrolein and protected DA-like cells in vitro.Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.Conclusions:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD.Considering the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health.展开更多
基金supported by the National Natural Science Foundation of China[grant numbers U1904209 andU2004102]the Open Project of the Third Affiliated Hospital of Xinxiang Medical University[fund number.KFKTZD202101]the Graduate Research Innovation Support Program of Xinxiang Medical University[grant Number.YJSCX202157Y].
文摘Gas explosion injury is a compound injury caused by a shock wave,high-temperature flame,or toxic gas directly or indirectly acting on the human body,resulting in multiple organ damage.As a hyperaerated tissue,the lung is the primary organ that experiences an early injury.The pathological manifestations of gas-explosion-induced acute lung injury(ALI)include pulmonary tissue edema.
基金supported by a grant from National Institute of Neurological Disorders and Stroke R21(No.1R21NS115094-01)。
文摘Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional loss.Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2(ALDH2),a key oxidoreductase and powerful endogenous anti-aldehyde machinery,is likely important for protecting neurons from aldehydesmediated degeneration.Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator(Alda-1),we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2.Over an acute 2 day period post injury,we found that ALDH2 expression was significantly lowered post-SCI,but not so in rats given Alda-1.This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction,which was revealed in co-immunoprecipitation experiments.We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord,and reduced cyst pathology.In addition,Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI.Finally,ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure.It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims.All animal work was approved by Purdue Animal Care and Use Committee(approval No.1111000095)on January 1,2021.
基金This work was supported by the National Institutes of Health(Grant#NS090244 and NS115094 to RS)as well as grants from the National Key Technology Support Program(2014BAI03B01 to Z.C)Sichuan International Science and Technology Innovation Cooperation Project(2020YFH0148 to Z.C).
文摘Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat model.As such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral benefits.Methods:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats.The acrolein levels and related pathologies were measured by immunohistochemistry.Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test.Pain was assessed using mechanical allodynia,cold hypersensitivity,and plantar tests.Finally,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.Results:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and cortex.DP also mitigated both motor and sensory deficits typical of PD.In addition,DP lowered acrolein and protected DA-like cells in vitro.Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.Conclusions:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD.Considering the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health.
