Neuroprotective effect and cognitive outcome of chronic lithium on traumatic brain injury in mice.
In vitro and in vivo studies have demonstrated that lithium treatment can protect neurons against excitotoxic and ischemic damage. Yet the possible beneficial effect of chronic low dose lithium on a model of traumatic brain injury (TBI) has not been intensively investigated. In this study, lithium (1 mmol/kg) was given daily, intraperitonealy, for 14 days before the onset of moderate controlled TBI and was continued until the mice were sacrificed. The results showed that in brain injured animals, chronic lithium treatment attenuated the loss of hemispheric tissue, cerebral edema and the expression of pro-inflammatory cytokine interleukin-1β. The neuronal degeneration in hippocampal CA3 and dentate gyrus sub-regions was also attenuated in the chronic lithium-treated mice as shown by Fluoro-Jade B staining. Moreover, chronic lithium treatment enhanced spatial learning and memory performance of injured mice in the Morris water maze. Our current study extended the protective role of lithium in the model of TBI and suggested that chronic lithium treatment might be a helpful therapeutic strategy for brain injury with multiple beneficial effects.
Zhu
Zu-Fu
ZF
Department of Neurology, The Affiliated Jiangyin Hospital, Medical College of Southeast University, China. zufuzhu@gmail.com
Wang
Qing-Guang
QG
Han
Bo-Jun
BJ
William
Callie P
CP
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009930:Organic Chemicals / Q000378:metabolism
D014150:Antipsychotic Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C435731:fluoro jade; D008094:Lithium