Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
AJVaccines, Copenhagen, Denmark.
Fluids Barriers CNS. 2018 Sep 25;15(1):27. doi: 10.1186/s12987-018-0111-8.
Cerebral edema can cause life-threatening increase in intracranial pressure. Besides surgical craniectomy performed in severe cases, osmotherapy may be employed to lower the intracranial pressure by osmotic extraction of cerebral fluid upon intravenous infusion of mannitol or NaCl. A so-called rebound effect can, however, hinder continuous reduction in cerebral fluid by yet unresolved mechanisms.
We determined the brain water and electrolyte content in healthy rats treated with osmotherapy. Osmotherapy (elevated plasma osmolarity) was mediated by intraperitoneal injection of NaCl or mannitol with inclusion of pharmacological inhibitors of selected ion-transporters present at the capillary lumen or choroidal membranes. Brain barrier integrity was determined by fluorescence detection following intravenous delivery of Na-fluorescein.
NaCl was slightly more efficient than mannitol as an osmotic agent. The brain water loss was only ~ 60% of that predicted from ideal osmotic behavior, which could be accounted for by cerebral Na and Cl accumulation. This electrolyte accumulation represented the majority of the rebound response, which was unaffected by the employed pharmacological agents. The brain barriers remained intact during the elevated plasma osmolarity.
A brain volume regulatory response occurs during osmotherapy, leading to the rebound response. This response involves brain accumulation of Na and Cl and takes place by unresolved molecular mechanisms that do not include the common ion-transporting mechanisms located in the capillary endothelium at the blood-brain barrier and in the choroid plexus epithelium at the blood-CSF barrier. Future identification of these ion-transporting routes could provide a pharmacological target to prevent the rebound effect associated with the widely used osmotherapy.
脑水肿可导致颅内压危及生命的增加。除了在严重情况下进行手术开颅术外，还可以通过静脉输注甘露醇或 NaCl 进行渗透治疗，通过渗透提取脑液来降低颅内压。然而，由于尚未解决的机制，所谓的反弹效应可能会阻碍颅内压的持续降低。
我们在接受渗透治疗的健康大鼠中测定了脑水和电解质含量。通过腹腔内注射 NaCl 或甘露醇来进行渗透治疗（升高血浆渗透压），并包括在毛细血管腔或脉络膜膜上存在的选定离子转运体的药理学抑制剂。通过静脉内给予 Na-荧光素后荧光检测来确定血脑屏障的完整性。
NaCl 作为渗透剂的效率略高于甘露醇。脑水丢失仅约为理想渗透行为预测值的 60%，这可以用脑内 Na 和 Cl 积累来解释。这种电解质积累代表了反弹反应的大部分，而所采用的药理学药物对其没有影响。在升高的血浆渗透压期间，血脑屏障保持完整。
在渗透治疗期间发生了脑容量调节反应，导致了反弹反应。这种反应涉及脑内 Na 和 Cl 的积累，并且通过尚未解决的分子机制发生，这些机制不包括位于血脑屏障毛细血管内皮和血脑脊液屏障脉络丛上皮的常见离子转运机制。未来对这些离子转运途径的鉴定可能为预防与广泛使用的渗透治疗相关的反弹效应提供药理学靶点。
Zotero 插件
