Purpose: Increasing evidence indicates that lithium is a neuroprotective agent against transient focal and global ischemic injury in the adult animal. In the developing brain, lithium has shown protective effects against neuroapoptosis induced by drugs. This study was designed to investigate the neuroprotective effects of lithium on hypoxic-ischemic brain injury in the neonatal rat.
Methods: Seven-day-old Sprague-Dawley rats underwent hypoxic-ischemic injury (HII) induced by ligation of the common carotid artery followed by exposure to ~2.5 h of hypoxia (~7% oxygen). After HII, rat pups were randomly assigned into two groups: a control group (n = 21), which received a daily subcutaneous injection of 0.9% normal saline for 14 days following HII; and a lithium group (n = 32), treated with daily injection of lithium chloride. N-acetylaspartate/creatinine, choline/creatinine, lipid/creatinine ratios at 1.3 ppm (Lip(1.3)/Cr) and 0.9 ppm (Lip(0.9)/Cr) lipid peaks were evaluated by proton magnetic resonance spectroscopy on the day of HII and on days 7 and 14 after HII. Infarct ratios based on magnetic resonance images were also determined at the same time points.
Results: Seven days after HII, the Lip(1.3)/Cr and Lip(0.9)/Cr ratios as well as the infarct ratio were significantly lower in the lithium group than in the control group. The Lip(1.3)/Cr and Lip(0.9)/Cr ratios were significantly correlated with infarct ratio.
Conclusion: This study showed that post-HII treatment with lithium may have a neuroprotective effect in the immature brain. Further studies are needed to elucidate the mechanism of neuroprotective properties of lithium against HII-induced neonatal brain damage.