Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China.
Theranostics. 2024 Sep 16;14(15):6053-6070. doi: 10.7150/thno.100982. eCollection 2024.
Subarachnoid hemorrhage (SAH) induced acute impairment of the glymphatic system, but few have investigated the dysfunction of the meningeal lymphatic system and their contribution to the pathophysiology of SAH. In addition, most studies were conducted in rodent animals. We aimed to investigate the impact of SAH on glymphatic and meningeal lymphatic function in a large animal model using beagles and to evaluate the effects of intermittent cistern magna CSF drainage on these systems. The SAH model was created in beagles via endovascular perforation using a digital subtraction angiography machine. Intermittent cistern magna CSF drain was performed daily from 1 d to 3 d after SAH. We examined CSF pressure, neuronal death, enlargement of perivascular space (PVS), hydrocephalus, and neurological and cognitive deficits before and after SAH. The dynamics of glymphatic and meningeal lymphatic functions were analyzed by quantifying the signal intensity of dimeglumine gadopentetate (Gd-DTPA) using T1-weighted magnetic resonance imaging (MRI). Measurements were taken before SAH and at 1 h, 1 week, and 2 weeks post-SAH. SAH in beagles caused significant blood clots, neuronal death, increased CSF pressure, hydrocephalus, and neurological and cognitive deficits. MRI revealed dilated ventricles and enlarged PVS post-SAH. The glymphatic system's function, assessed by Gd-DTPA distribution, showed reduced CSF influx and glymphatic impairment after SAH, particularly in the ipsilateral hemisphere, persisting for a week with partial recovery at 2 weeks. For lymphatic clearance, Gd-DTPA rapidly filled the olfactory bulbs, optic nerves, facial and vestibulocochlear nerves, and spinal nerves under normal conditions. SAH caused delayed and reduced Gd-DTPA efflux outflow in these areas, disrupting lymphatic clearance. Despite initial dysfunction, increased hemoglobin levels in cervical lymph nodes indicated active blood clearance post-SAH, with recovery by 2 weeks. Treatment with intermittent cistern magna CSF drain significantly ameliorated the glymphatic and meningeal lymphatic dysfunction after SAH. SAH impaired both glymphatic and meningeal lymphatic functions in beagles, with better restoration of lymphatic function post-SAH, which may contribute to functional recovery after SAH. External CSF drain is an effective therapeutic approach to facilitate the recovery of glymphatic and meningeal lymphatic function following SAH.
蛛网膜下腔出血 (SAH) 可导致脑淋巴系统急性损伤，但很少有研究探讨脑膜淋巴系统的功能障碍及其对 SAH 病理生理学的影响。此外，大多数研究都是在啮齿动物中进行的。我们的目的是使用比格犬研究 SAH 对大动物模型中脑淋巴和脑膜淋巴功能的影响，并评估间歇性脑池蛛网膜下腔脑脊液引流对这些系统的影响。通过数字减影血管造影机，使用血管内穿孔的方法在比格犬中创建了 SAH 模型。SAH 后 1 天至 3 天，每日进行间歇性脑池蛛网膜下腔脑脊液引流。我们在 SAH 前后检查了脑脊液压力、神经元死亡、血管周围间隙 (PVS) 扩大、脑积水以及神经和认知缺陷。通过定量分析二甲基葡胺钆喷替酸（Gd-DTPA）的信号强度，使用 T1 加权磁共振成像（MRI）分析脑淋巴和脑膜淋巴功能的动力学。在 SAH 前以及 SAH 后 1 小时、1 周和 2 周进行测量。比格犬的 SAH 导致明显的血栓形成、神经元死亡、脑脊液压力升高、脑积水和神经认知缺陷。MRI 显示 SAH 后脑室扩大和 PVS 扩大。通过 Gd-DTPA 分布评估的脑淋巴系统功能显示，SAH 后 CSF 流入减少和脑淋巴功能障碍，特别是在同侧半球，持续 1 周，2 周时部分恢复。对于淋巴清除，在正常情况下，Gd-DTPA 迅速充满嗅球、视神经、面部和前庭耳蜗神经以及脊神经。SAH 导致这些区域的 Gd-DTPA 流出流出延迟和减少，破坏了淋巴清除。尽管最初存在功能障碍，但颈淋巴结中血红蛋白水平的增加表明 SAH 后存在主动血液清除，2 周时恢复。间歇性脑池蛛网膜下腔脑脊液引流治疗可显著改善 SAH 后脑淋巴和脑膜淋巴功能障碍。SAH 损害了比格犬的脑淋巴和脑膜淋巴功能，SAH 后淋巴功能恢复更好，这可能有助于 SAH 后的功能恢复。外部脑脊液引流是一种有效的治疗方法，可促进 SAH 后脑淋巴和脑膜淋巴功能的恢复。
