PDF(Pubmed)
Abstract：
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved.
METHODS: We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics.
RESULTS: Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats.
CONCLUSIONS: Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.
METHODS: We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics.
RESULTS: Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats.
CONCLUSIONS: Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.
摘要：
背景：特发性颅内高压（IIH）是一种表现出颅内压（ICP）升高的综合征，视觉障碍,和严重的头痛。IIH主要影响年轻肥胖女性，尽管它可以发生在任何年龄的人身上，BMI,和性爱。IIH的特征是全身性代谢失调，雄激素激素增加。然而,肥胖/激素扰动对脑脊液(CSF)动力学的影响仍未解决.
方法：我们使用肥胖雌性Zucker大鼠和佐剂睾酮来揭示IIH因果驱动因素。通过体内实验和磁共振成像确定ICP和CSF动力学，用质谱法评估睾酮水平，转录组学揭示了脉络丛的功能。
结果：肥胖大鼠的CSF睾酮水平未受干扰，ICP或CSF动力学无变化。佐剂睾酮治疗肥胖大鼠提高脑脊液分泌率,虽然对ICP没有影响，由于这些大鼠的脑脊液引流能力升高。
结论：肥胖本身不足以概括大鼠的IIH症状，但是CSF动力学的调节出现在辅助睾酮治疗中，这模拟了女性IIH患者中观察到的雄激素过量。因此，肥胖诱导的雄激素失调可能导致IIH的疾病机制，并可能作为未来的治疗靶标。
方法：我们使用肥胖雌性Zucker大鼠和佐剂睾酮来揭示IIH因果驱动因素。通过体内实验和磁共振成像确定ICP和CSF动力学，用质谱法评估睾酮水平，转录组学揭示了脉络丛的功能。
结果：肥胖大鼠的CSF睾酮水平未受干扰，ICP或CSF动力学无变化。佐剂睾酮治疗肥胖大鼠提高脑脊液分泌率,虽然对ICP没有影响，由于这些大鼠的脑脊液引流能力升高。
结论：肥胖本身不足以概括大鼠的IIH症状，但是CSF动力学的调节出现在辅助睾酮治疗中，这模拟了女性IIH患者中观察到的雄激素过量。因此，肥胖诱导的雄激素失调可能导致IIH的疾病机制，并可能作为未来的治疗靶标。
