Short-term lithium treatment protects the brain against ischemia–reperfusion injury by enhancing the neuroplasticity of cortical neurons

Shih Huang Tai, Liang Chun Chao, Tung Yi Huang, Che Chao Chang, Sheng Yang Huang, Tian Shung Wu, E. Jian Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Objectives: Lithium exerts a broad neuroprotective effect on the brain. This study examined whether lithium exerts therapeutic effects on stroke by restoring neural connections at the ischemic core of cortices post brain insult. Methods: We treated rats with lithium or vehicle (saline) every 24 h for the first 72 h, starting at the beginning of reperfusion after inducing middle cerebral artery occlusion (MCAO) in rats. Somatosensory evoked potential (SSEP) recording and behavioral testing were employed to evaluate the beneficial effects of lithium treatment. To examine the effects of lithium-induced neuroplasticity, we evaluated the dendritic morphology in cortex pyramidal cells and the primary neuronal cell culture that underwent brain insults and oxygen and glucose deprivation (OGD), respectively. Results: The results demonstrated that rats subjected to MCAO had prolonged N1 latency and a decreased N1/P1 amplitude at the ipsilateral cortex. Four doses of lithium reduced the brain infarction volume and enhanced the SSEP amplitude. The results of neurobehavioral tests demonstrated that lithium treatment improved sensory function, as demonstrated by improved 28–point clinical scale scores. In vitro study results showed that lithium treatment increased the dendritic lengths and branches of cultured neurons and reversed the suppressive effects of OGD. The in vivo study results indicated that lithium treatment increased cortical spine density in various layers and resulted in the development of the dendritic structure in the contralateral hemisphere. Conclusion: Our study confirmed that neuroplasticity in cortical neurons is crucial for lithium-induced brain function 50 recovery after brain ischemia.

Original languageEnglish
Pages (from-to)128-138
Number of pages11
JournalNeurological Research
Issue number2
Publication statusPublished - 2022

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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