Glymphatic transport is reduced in rats with spontaneous pituitary tumor.

Glymphatic transport is reduced in rats with spontaneous pituitary tumor.
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DOI:
10.3389/fmed.2023.1189614
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发表时间:
2023
影响因子:
3.9
通讯作者:
--
中科院分区:
医学3区
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患者中的垂体瘤会引起大脑的不良改变,并伴有认知缺陷。胶质淋巴废物清除功能障碍导致神经毒性产物在脑内积聚,从而导致认知障碍。然而,垂体瘤患者脑内胶质淋巴功能的状态尚不清楚。利用磁共振成像(MRI)和先进的数学模型,研究了自发性垂体瘤大鼠胶质淋巴转运的变化。大鼠(22-24个月,雌性,Wistar),有和没有垂体瘤(n = 7/每组)进行了相同的实验方案。对每只动物进行MRI测量,包括T2加权成像和脑池内注射造影剂的动态3D T1加权成像。动态图像上观察到Willis环和胶质淋巴流入淋巴结内的造影剂诱导增强,并用时间-信号曲线(TSCs)进行验证。在多个代表性脑区域中评价了表征胶质淋巴示踪剂转运动力学的输注速率和清除速率的模型衍生参数。我们的影像学资料显示Willis环部分强化的发生率较高(86对14%; P < 0.033),垂体胶质淋巴流入淋巴结增强的发生率较低(71 vs. 100%)和松果体(57 vs.86%)的大鼠垂体瘤比正常垂体外观的大鼠的隐窝,表明由于垂体瘤的存在,血管周围通路受损和胶质淋巴转运受阻的加剧。一致的是,我们的动力学建模和局部脑组织定量显示,与非肿瘤大鼠相比,自发性垂体瘤大鼠所有检查区域的输注和清除率均显著降低,这表明垂体瘤大鼠脑中的胶质淋巴转运受到抑制。我们的研究表明,受损的胶质淋巴运输在大鼠脑与自发性垂体瘤。脑废物清除效率降低增加了脑神经退行性变的风险,这可能是垂体瘤患者常见的认知障碍的基础。
Pituitary tumor in patients induces adverse alterations in the brain, accompanied by cognitive deficits. Dysfunction of glymphatic waste clearance results in accumulation of neurotoxic products within the brain, leading to cognitive impairment. However, the status of glymphatic function in the brain with pituitary tumor is unknown. Using magnetic resonance imaging (MRI) and an advanced mathematical modeling, we investigated the changes of glymphatic transport in the rats carrying spontaneous pituitary tumor. Rats (22–24 months, female, Wistar) with and without pituitary tumor (n = 7/per group) underwent the identical experimental protocol. MRI measurements, including T2-weighted imaging and dynamic 3D T1-weighted imaging with intracisternal administration of contrast agent, were performed on each animal. The contrast-induced enhancement in the circle of Willis and in the glymphatic influx nodes were observed on the dynamic images and verified with time-signal-curves (TSCs). Model-derived parameters of infusion rate and clearance rate that characterize the kinetics of glymphatic tracer transport were evaluated in multiple representative brain regions. Our imaging data demonstrated a higher incidence of partially enhanced circle of Willis (86 vs. 14%; p < 0.033) and a lower incidence of enhancement in glymphatic influx nodes of pituitary (71 vs. 100%) and pineal (57 vs. 86%) recesses in the rats with pituitary tumor than in the rats with normal appearance of pituitary gland, indicating an intensification of impaired peri-vascular pathway and impeded glymphatic transport due to the presence of pituitary tumor. Consistently, our kinetic modeling and regional cerebral tissue quantification revealed significantly lower infusion and clearance rates in all examined regions in rats with spontaneous pituitary tumor than in non-tumor rats, representing a suppressed glymphatic transport in the brain with pituitary tumor. Our study demonstrates the compromised glymphatic transport in the rat brain with spontaneous pituitary tumor. The reduced efficiency in cerebral waste clearance increases the risk for neurodegeneration in the brain that may underlie the cognitive impairment commonly seen in patients with pituitary tumors.
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