Aquaporin-4 (AQP4), a predominant water channel of the brain, mediates transmembrane water movement at the blood-brain barrier and brain-cerebrospinal fluid interface. A broad pattern of evidence indicates that AQP4 and regulators of its expression are potential targets for treatment of brain swelling, but whether it participates in the regulation of neurotransmission has not been reported. We examined neurochemical differences between AQP4-knockout and wild-type mice with particular focus on neurotransmission. Basal tissue neurotransmitter and metabolite levels were measured by high-performance liquid chromatography. Significant sex- and region-specific differences of amino acids and monoamines were found in the brain of wild-type and AQP4-knockout mice. In cortex, striatum, and hippocampus of male AQP4-knockout mice, an increase of glutamine and decrease of aspartate were observed. Glutamate was increased only in female AQP4-knockout mice. The lack of AQP4 failed to affect the levels of gamma-aminobutyric acid and taurine. In the medial prefrontal cortex of AQP4-knockout mice, the levels of serotonin and norepinephrine were increased, but no significant change in dopamine level was found. In the striatum of male AQP4-knockout mice, the levels of dopamine and serotonin were remarkably increased, which was not found in female mice. In the hypothalamus of AQP4-knockout mice, only the serotonin level was altered. These results provide the first evidence that the lack of AQP4 expression is accompanied by sex- and region-specific alterations in brain amino acid and monoamine metabolism.

BackgroundConcurrent chemoradiotherapy is a standard treatment for local advanced esophageal cancer, but the outcomes are controversial. Our goals were to compare the therapeutic effects of concurrent chemoradiotherapy and radiotherapy alone in local advanced esophageal cancer using meta-analysis.MethodsMEDLINE, EMBASE and the Cochrane library were searched for studies comparing chemoradiotherapy with radiotherapy alone for advanced esophageal cancer. Only randomized controlled trials were included, and extracted data were analyzed with Review Manager Version 5.2. The pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated for statistical analysis.ResultsNine studies were included. Of 1,135 cases, 612 received concurrent chemoradiotherapy and 523 were treated with radiotherapy alone. The overall response rate (complete remission and partial remission) was 93.4% for concurrent chemoradiotherapy and 83.7% for radiotherapy alone (P = 0.05). The RR values of 1-year, 3-year, and 5-year survival rates were 1.14 (95% CI: 1.04 - 1.24, P = 0.006), 1.66 (95% CI: 1.34 - 2.06, P < 0.001), and 2.43 (95% CI: 1.63 - 3.63, P < 0.001), respectively. The RR value of the merged occurrence rate of acute toxic effects was 2.34 (95% CI: 1.90 - 2.90, P <0.001). There was no difference in the incidence of late toxic effects, which had an RR value of 1.21 (95% CI: 0.96 - 1.54, P = 0.11). The RR level of persistence and recurrence was 0.71 (95% CI: 0.62 - 0.81, P <0.001), and for the distant metastasis rate, the RR value was 0.79 (95% CI: 0.61 - 1.02, P = 0.07).ConclusionsConcurrent chemoradiotherapy significantly improved overall survival rate, reduced the risk of persistence and recurrence, but had little effect on the primary tumor response, and increased the occurrence of acute toxic effects.

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