Reduction of neuroinflammation alleviated mouse post bone fracture and stroke memory dysfunction.

Abstract

Tibia fracture (BF) enhances stroke injury and post-stroke memory dysfunction in mouse. Reduction of neuroinflammation by activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) reduced acute neuronal injury and sensorimotor dysfunction in mice with BF 1-day after stroke. We hypothesize that reduction of neuroinflammation by activation of α-7 nAchR improves long-term memory function of mice with BF 6-h before stroke. The mice were randomly assigned to saline, PHA-568487 (α-7 nAchR agonist) and methyllycaconitine (antagonist) treatment groups. The sensorimotor function was tested by adhesive removal and corner tests at 3 days, the memory function was tested by Y-maze test weekly for 8 weeks and novel objective recognition test at 8 weeks post-injuries. We found PHA-568487 treatment reduced, methyllycaconitine increased the number of CD68+ cells in the peri-infarct and hippocampal regions, neuronal injury in the infarct region, sensorimotor and long-term memory dysfunctions. PHA-568487 treatment also reduced, while methyllycaconitine treatment increased atrophy of hippocampal granule cell layer and white matter damage in the striatum. In addition, PHA-568487 treatment increased neuron proliferation in granule cell layer. Our data indicated that reduction of neuroinflammation through activation of α-7 nAchR decreased neuronal damage, sensorimotor and long-term memory dysfunction of mice with BF shortly before stroke.

• Authors: Kang Huo, Meng Wei, Meng Zhang, Zhanqiang Wang, Peipei Pan, Sonali S Shaligram, Jinhao Huang, Leandro B Do Prado, Julia Wong, Hua Su
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 41 Issue 9 Pg. 2162-2173 (09 2021) ISSN: 1559-7016 [Electronic] United States
• PMID: 33641516 (Publication Type: Journal Article)

Topics

• Animals
• Disease Models, Animal
• Female
• Fractures, Bone (etiology, pathology)
• Humans
• Inflammation (therapy)
• Male
• Memory, Long-Term (physiology)
• Mice
• Stroke (complications, therapy)