ligustilide and Postoperative-Cognitive-Complications

Ligustilide exerts potential neuroprotective effects against various cerebral ischaemic insults and neurodegenerative disorders. However, the function and mechanisms of LIG-mediated hippocampal neural stem cells (H-NSCs) activation as well as cognitive recovery in the context of post-operative cognitive dysfunction (POCD) remain elusive and need to be explored. Mice were subjected to transient global cerebral ischaemia and reperfusion (tGCI/R) injury and treated with LIG (80 mg/kg) or vehicle for 1 month. Morris water maze test and western blot were employed to assess cognitive function. Nissl staining and immunofluorescence (IF) staining were used to detect H-NSCs proliferation and neurogenesis in hippocampus. Subsequently, primary H-NSCs were treated with LIG, and the level of H-NSCs proliferation and neuronal-differentiation was examined by IF staining for Edu and β-Tubulin III. The protein levels of ERK1/2, β-catenin, NICD, TLR4, Akt and FoxO1 were examined using western blotting. Finally, pretreatment with the ERK agonist SCH772984 was performed to observe the change in ERK expression. LIG treatment promoted H-NSCs proliferation and neurogenesis, increased the number of neurons in the hippocampal subfields, and ultimately reversed cognitive impairment in tGCI/R injury. Furthermore, LIG also promoted primary H-NSCs proliferation and neuronal-differentiation, as well as ERK1/2 phosphorylation. Pretreatment with SCH772984 effectively reversed the ability of LIG to induce ERK1/2 phosphorylation and promote H-NSCs proliferation and neuronal-differentiation. LIG can promote cognitive recovery after tGCI/R injury by activating ERK1/2 in H-NSCs to promote their proliferation and neurogenesis in the hippocampus. Therefore, LIG has potential for use in the prevention and/or treatment of POCD.

Topics: 4-Butyrolactone; Animals; Cell Proliferation; Cognition; Hippocampus; Mice; Neural Stem Cells; Neurogenesis; Postoperative Cognitive Complications