Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there a...Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there are no effective treatments to directly resolve edema within the spinal cord.The aquaporin-4(AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal.Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma.With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration.Inevitably, several injury models have been developed(contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results.This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present(vasogenic vs cytotoxic).Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery.Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.展开更多
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse tra...To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.展开更多
Aquaporin-0 (AQP0) contributes to the nurturing and cleaning of the eye lens of waste products. It is a tetrameric protein composed of four identical monomers, each of which has its own water pore. AQP0 water conducti...Aquaporin-0 (AQP0) contributes to the nurturing and cleaning of the eye lens of waste products. It is a tetrameric protein composed of four identical monomers, each of which has its own water pore. AQP0 water conduction is regulated by pH, Ca<sup>2+</sup> concentration, and the phosphorylation of serine residues at the C-terminal. High cellular Ca<sup>2+</sup> concentration enhances the binding of Calmodulin (CaM), a Ca<sup>2+</sup> dependent protein, to AQP0 from cytoplasm. This study focuses on determining the differences between the AQP0-CaM and the open AQP0 systems, by using Molecular Dynamics (MD) methods. The water conduction energy profiles are measured with two separate MD simulation techniques revealed two distinct channel profiles for the AQP0-CaM combined model. While the CaM bound channels’ energy barriers exceed the 6 kcal/mol, the no CaM bound AQP0 energy profile stays below 3 kcal/mol. The structural analysis of these different pores during the free equilibrations also supported this conclusion with distinct pore diameters. Unlike the previous report, this study observed Phe75 and His66 taking role in stabilizing the CSII restriction site in CaM bound AQP0.展开更多
文摘Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there are no effective treatments to directly resolve edema within the spinal cord.The aquaporin-4(AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal.Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma.With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration.Inevitably, several injury models have been developed(contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results.This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present(vasogenic vs cytotoxic).Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery.Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.
基金supported by a grant for Scientific Research Program from the Health Bureau of Henan Province (No.200202)
文摘To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.
文摘Aquaporin-0 (AQP0) contributes to the nurturing and cleaning of the eye lens of waste products. It is a tetrameric protein composed of four identical monomers, each of which has its own water pore. AQP0 water conduction is regulated by pH, Ca<sup>2+</sup> concentration, and the phosphorylation of serine residues at the C-terminal. High cellular Ca<sup>2+</sup> concentration enhances the binding of Calmodulin (CaM), a Ca<sup>2+</sup> dependent protein, to AQP0 from cytoplasm. This study focuses on determining the differences between the AQP0-CaM and the open AQP0 systems, by using Molecular Dynamics (MD) methods. The water conduction energy profiles are measured with two separate MD simulation techniques revealed two distinct channel profiles for the AQP0-CaM combined model. While the CaM bound channels’ energy barriers exceed the 6 kcal/mol, the no CaM bound AQP0 energy profile stays below 3 kcal/mol. The structural analysis of these different pores during the free equilibrations also supported this conclusion with distinct pore diameters. Unlike the previous report, this study observed Phe75 and His66 taking role in stabilizing the CSII restriction site in CaM bound AQP0.
