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  • In addition to the increase of extracellular glutamate ICH

    2021-09-14

    In addition to the increase of extracellular glutamate, ICH can also increase the levels of reactive oxygen species (ROS) and oxidative stress. Although the products of red blood cell lysis and plasma components, as well as the excitotoxic effect of glutamate have been to increase oxidative damage (Ha and Park, 2006; Hu et al., 2016; Lo et al., 2003), there is no description of the temporal profile of glial glutamate uptake activity and oxidative changes occurring after ICH. The collagenase-induced ICH model is a commonly used method to mimic hematoma expansion in rodents mirroring the clinical situation. During 4–24 h after the injection of bacterial collagenase into the basal ganglia a full hematoma develops through the breakdown of basal lamina of blood vessels. This is a simple and reproducible method that runs from in situ vessels. Nonetheless, its limitation is that collagenase injures many blood vessels depending on the dosing and diffusion characteristics, resulting in a diffuse blood pattern throughout the parenchyma producing greater and extended lesion long after the onset of EZ Cap Reagent AG synthesis injection (Kirkman et al., 2011; MacLellan et al., 2008). Considering the importance of glutamate uptake in the pathogenesis of intracerebral hemorrhage and the fact that glutamatergic excitotoxicity and oxidative stress are events individually described in the literature, it is important to understand how they interact during the establishment of ICH mechanisms of lesion. The present study aims to describe the temporal profile of glial glutamate transporters, the glutamate uptake activity and the oxidative status changes into the striatum after intracerebral hemorrhage in the rat. For this purpose, the expression of EAAT1 and EAAT2 glial transporters, glutamate uptake, glutamine synthetase and Na+/K+-ATPase activities, the oxidative profile and the neuronal cell loss were evaluated at 6 h, 24 h, 72 h and 7 days after a collagenase-induced intracerebral hemorrhage in the rat striatum (Mestriner et al., 2011; Neves et al., 2017).
    Materials and methods
    Statistics Statistical analysis was performed using SPSS 23 for Windows (Package for the Social Sciences, Inc., Chicago, USA). Data are expressed as mean ± standard error of the mean (SEM). Results of biochemical parameters presented normal distribution (as confirmed by the Shapiro-Wilk normality test) and were analyzed by means of one-way ANOVA analysis, followed by the Duncan post hoc test whenever indicated. Differences were considered significant whenever P ≤ 0.05. Sample size calculation was based on previous studies with similar methodology for biochemical analysis (Nakamura et al., 2005; Qureshi et al., 2003) in order to reach the statistical power of 80% calculated with the software PEPI for-Windows 4.0.
    Results
    Discussion Present work investigated the temporal changes of glutamate transporters expression, glutamate uptake, Na+/K+-ATPase and GS activities, the oxidative profile and the percentage of neuronal cells of rat striatum after ICH. Main results show that collagenase-induced ICH produced a distinct expression pattern of EAAT1 and EAAT2, and of glutamate uptake activity. EAAT1 expression and glutamate uptake decreased at 6 h, whereas EAAT2 decreased at 72 h; interestingly, 7 days after ICH, EAAT2 expression increased in parallel with the glutamate uptake activity (Fig. 3). The oxidative stress, as assessed by TBARS and DCF, and endogenous defense system (SOD, Cat, GPx and GSH) exhibited a remarkable response at 72 h post-ICH (Fig. 4). Intracerebral hemorrhage also increased Na+/K+-ATPase activity and decreased GS activity; these enzymes are known to be important contributors for the glial glutamate transporters. Altogether, present results indicate that ICH induces, in a time-dependent manner, different EAAT1 and EAAT2 responses, culminating with an imbalance of glutamate uptake capacity and increased oxidative stress, possibly associated to sustained neuronal loss (Fig. 5).