| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Chiou, Shene Yi-Shiuan Kysenius, Kai Huang, Yifan Habgood, Mark David Koehn, Liam M. Qiu, Fiona Crouch, Peter J. Varshney, Swati Ganio, Katherine Dziegielewska, Katarzyna Magdalena Saunders, Norman Ruthven |
| Abstract | Background Little is known about the extent of drug entry into developing brain, when administered to pregnant and lactating women. Lithium is commonly prescribed for bipolar disorder. Here we studied transfer of lithium given to dams, into blood, brain and cerebrospinal fluid (CSF) in embryonic and postnatal animals as well as adults. Methods Lithium chloride in a clinically relevant dose (3.2 mg/kg body weight) was injected intraperitoneally into pregnant (E15–18) and lactating dams (birth-P16/17) or directly into postnatal pups (P0–P16/17). Acute treatment involved a single injection; long-term treatment involved twice daily injections for the duration of the experiment. Following terminal anaesthesia blood plasma, CSF and brains were collected. Lithium levels and brain distribution were measured using Laser Ablation Inductively Coupled Plasma-Mass Spectrometry and total lithium levels were confirmed by Inductively Coupled Plasma-Mass Spectrometry. Results Lithium was detected in blood, CSF and brain of all fetal and postnatal pups following lithium treatment of dams. Its concentration in pups’ blood was consistently below that in maternal blood (30–35%) indicating significant protection by the placenta and breast tissue. However, much of the lithium that reached the fetus entered its brain. Levels of lithium in plasma fluctuated in different treatment groups but its concentration in CSF was stable at all ages, in agreement with known stable levels of endogenous ions in CSF. There was no significant increase of lithium transfer into CSF following application of Na+/K+ ATPase inhibitor (digoxin) in vivo, indicating that lithium transfer across choroid plexus epithelium is not likely to be via the Na+/K+ ATPase mechanism, at least early in development. Comparison with passive permeability markers suggested that in acute experiments lithium permeability was less than expected for diffusion but similar in long-term experiments at P2. Conclusions Information obtained on the distribution of lithium in developing brain provides a basis for studying possible deleterious effects on brain development and behaviour in offspring of mothers undergoing lithium therapy. |
| Related Links | https://fluidsbarrierscns.biomedcentral.com/counter/pdf/10.1186/s12987-021-00285-w.pdf |
| Ending Page | 19 |
| Page Count | 19 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20458118 |
| DOI | 10.1186/s12987-021-00285-w |
| Journal | Fluids and Barriers of the CNS |
| Issue Number | 1 |
| Volume Number | 18 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2021-12-07 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Hematology Neurobiology Pregnancy Bipolar-disorder prophylaxis Placental transfer Postnatal Brain barriers Cerebrospinal fluid |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Developmental Neuroscience Medicine Cellular and Molecular Neuroscience |
| Journal Impact Factor | 5.9/2023 |
| 5-Year Journal Impact Factor | 7.5/2023 |
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