Lithium pretreatment reduces brain injury after intracerebral hemorrhage in rats

Objective: In addition to the mood-stabilizing effects of lithium in patients with bipolar disorder, recent in vitro and in vivo studies in rodents increasingly implicate that lithium may be useful for treating acute cerebral ischemia, neuroinflammatory conditions, and chronic neurodegenerative diseases. However, whether lithium has a protective effect against hemorrhagic stroke is yet unknown. To test this possibility, we attempted to determine lithium's effect on experimental intracerebral hemorrhage (ICH). Methods: We treated adult rats with either lithium (2 mEq/kg) or saline for 3 days before inducing ICH via a stereotaxic infusion of collagenase into the left basal ganglia. Hematoma volumes, hemispheric swelling, long-term hemispheric atrophy, microglial activation, cell death, cyclooxygenase-2 expression, and behavioral outcomes were assessed. Results: Per behavioral tests 2 days after ICH, the lithium-treated group recovered better than did the saline-treated group. Three days after ICH, the hematoma volumes did not differ between the groups, but hemispheric swelling was less in the lithium-treated group. Forty-two days after ICH, hemispheric atrophy was less in the lithium-treated group. Lithium reduced cell death, cyclooxygenase-2 expression, and reactive microglia in the perihematomal regions. Conclusion: The present study shows that lithium, via anti-inflammation, reduces the perihematomal cell death, which is associated with sensorimotor recovery after experimental ICH.