Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are release...Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α and interleukin-1β participated in this hypoxic process. Moreover, when hypoxic injury occurred in the hippocampus, the release of interleukin-1α and interleukin-1β was mediated by the P2X4 receptor and P2X7 receptor. Immunofluorescence staining revealed that during ischemia/hypoxia, the P2X4 receptor, P2X7 receptor, interleukin-1α and interleukin-1β expression was detectable in rat hippocampal microglia, but only P2X4 receptor and P2X7 receptor expression was detected in astrocytes. Results suggested that the P2X4 receptor and P2X7 receptor, respectively, mediated interleukin-1α and interleukin-1β released by microglia, resulting in hippocampal ischemic/hypoxic injury. Astrocytes were activated, but did not synthesize or release interleukin-1α and interleukin-1β.展开更多
Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investig...Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investigate whether P2X7 receptor （P2X7R） is responsible for the CIH-induced neural injury and the possible pathway it involves.Methods：Eight-week-old male C57BL/6 mice were used.For each exposure time point,eight mice divided in room air （RA） and IH group were assigned to the study of P2X7R expression.Whereas in the 21 days-Brilliant Blue G （BBG,a selective P2X7R antagonist） study,48 mice were randomly divided into CIH group,BBG-treated CIH group,RA group and BBG-treated RA group.The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction （PCR）.The spatial learning was analyzed by Morris water maze.The nuclear factor kappa B （NFκB） and NADPH oxidase 2 （NOX2） expressions were analyzed by Westem blotting.The expressions of tumor necrosis factor α,interleukin 1 β （IL-β）,IL-18,and IL-6 were measured by real-time PCR.The malondialdehyde and superoxide dismutase levels were detected by colorimetric method.Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.Results：The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure.In the BBG study,the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test.The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group.BBG alleviated CIH-induced neural injury and consequent functional deficits.Conclusions：The P2X7R antagonism attenuates the CIH-induced neuroinflammation,oxidative stress,and spatial deficits,demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.展开更多
P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of ne...P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.展开更多
The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusi...The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.展开更多
Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the ve...Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch(BmK).We found that the expression of P2X7 receptors(P2X7Rs)was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats.P2X7R was selectively localized in microglia but not astrocytes or neurons.Similarly,interleukin 1β(IL-1β)was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection.Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors,and the up-regulation of P2X7R and IL-1β in the spinal cord.These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn,and therefore contributes to the development of BmK I-induced pain.展开更多
基金supported by the grants from the National Natural Science Foundation of China(No.3086008631060139and81171184)+5 种基金the Technology Pedestal and Society Development Project of Jiangxi ProvinceChina(No.2010BSA09500)the Young Scholars Science Foundation of Jiangxi ProvinceChina(No.20122BAB215005)the Youth Science Foundation of the Education Department of Jiangxi ProvinceChina(No.GJJ12149)
基金supported by the Natural Science Foundation of Guangdong Province,No.S2011010004096
文摘Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α and interleukin-1β participated in this hypoxic process. Moreover, when hypoxic injury occurred in the hippocampus, the release of interleukin-1α and interleukin-1β was mediated by the P2X4 receptor and P2X7 receptor. Immunofluorescence staining revealed that during ischemia/hypoxia, the P2X4 receptor, P2X7 receptor, interleukin-1α and interleukin-1β expression was detectable in rat hippocampal microglia, but only P2X4 receptor and P2X7 receptor expression was detected in astrocytes. Results suggested that the P2X4 receptor and P2X7 receptor, respectively, mediated interleukin-1α and interleukin-1β released by microglia, resulting in hippocampal ischemic/hypoxic injury. Astrocytes were activated, but did not synthesize or release interleukin-1α and interleukin-1β.
基金grants from the National Natural Science Foundation of China （No. 81370185 and No. 81070067）.
文摘Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investigate whether P2X7 receptor （P2X7R） is responsible for the CIH-induced neural injury and the possible pathway it involves.Methods：Eight-week-old male C57BL/6 mice were used.For each exposure time point,eight mice divided in room air （RA） and IH group were assigned to the study of P2X7R expression.Whereas in the 21 days-Brilliant Blue G （BBG,a selective P2X7R antagonist） study,48 mice were randomly divided into CIH group,BBG-treated CIH group,RA group and BBG-treated RA group.The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction （PCR）.The spatial learning was analyzed by Morris water maze.The nuclear factor kappa B （NFκB） and NADPH oxidase 2 （NOX2） expressions were analyzed by Westem blotting.The expressions of tumor necrosis factor α,interleukin 1 β （IL-β）,IL-18,and IL-6 were measured by real-time PCR.The malondialdehyde and superoxide dismutase levels were detected by colorimetric method.Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.Results：The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure.In the BBG study,the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test.The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group.BBG alleviated CIH-induced neural injury and consequent functional deficits.Conclusions：The P2X7R antagonism attenuates the CIH-induced neuroinflammation,oxidative stress,and spatial deficits,demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.
基金financially supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HM046(to ZCZ),ZR2015HL113(to XJD),and ZR2014HL101(to XYW)the Science and Technology Development Project of Taian City of China,No.2015NS2183(to XJD)
文摘P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.
基金financially supported by grants from the National Natural Science Foundation of China,No.81371346,81271376Outstanding Postgraduate Fund of Xinxiang Medical UniversityScience and Technology Key Research Project of Henan Provincial Education Department of China,No.14A310019
文摘The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.
基金supported by grants from the National Natural Science Foundation of China (31571032 and 31771191)supported by an Indiana Spinal Cord and Brain Injury Research Fund grant from Indiana State Department of Health, USA (2017)
文摘Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch(BmK).We found that the expression of P2X7 receptors(P2X7Rs)was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats.P2X7R was selectively localized in microglia but not astrocytes or neurons.Similarly,interleukin 1β(IL-1β)was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection.Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors,and the up-regulation of P2X7R and IL-1β in the spinal cord.These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn,and therefore contributes to the development of BmK I-induced pain.
