Combined use of spatial restraint stress and middle cerebral artery occlusion is a novel model of post-stroke depression in mice.

Abstract

Post stroke depression (PSD) is one of the most common complications of ischemic stroke. At present, the underlying mechanisms are unclear, largely because there are no reliable, valid and reproducible animal models of PSD. Here we report a novel animal model of PSD that displays consistent and reliable clinical features of hemiplegic stroke. The animal model encompasses a combination of the middle cerebral artery occlusion (MCAO) and spatial restraint stress. We found that a 60-minute MCAO followed by spatial restraint stress for 2 h daily for 2 to 4 weeks from the fourth day after MCAO induced PSD-like depressive phenotypes in mice. Importantly, the mice showed exacerbated deficits of neurological functions and decreased body weights, which were accompanied with reduced levels of brain derived neurotrophic factor and neurotransmitters including serotonin and dopamine. In addition, we identified increased levels of serum cortisol in our PSD mice. Finally, we found that mice with PSD were responsive to the tri-cyclic antidepressant imipramine as evidenced by their attenuated depressive behaviors, increased body weights, recovered brain serotonin levels, and decreased serum cortisol levels. This mouse model replicates multiple features of human post-stroke depression and thus provides a new model for the investigation of PSD.

• Authors: Gaocai Zhang, Li Chen, Lingli Yang, Xiaodong Hua, Beiqun Zhou, Zhigang Miao, Jizhen Li, Hua Hu, Michael Namaka, Jiming Kong, Xingshun Xu
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16751 (Nov 17 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26572587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents, Tricyclic
• Brain-Derived Neurotrophic Factor
• Serotonin
• Imipramine
• Dopamine
• Hydrocortisone

Topics

• Animals
• Antidepressive Agents, Tricyclic (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Body Weight (drug effects)
• Brain (metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Depression (drug therapy, etiology, metabolism)
• Disease Models, Animal
• Dopamine (metabolism)
• Hydrocortisone (blood)
• Imipramine (pharmacology, therapeutic use)
• Infarction, Middle Cerebral Artery (complications)
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Inbred ICR
• Restraint, Physical
• Serotonin (metabolism)
• Stroke (complications)