Activated AMPK Protects Against Chronic Cerebral Ischemia in Bilateral Carotid Artery Stenosis Mice

• Published in: Cellular and molecular neurobiology Vol. 43; no. 5; pp. 2325 - 2335
• Main Authors: Xie, Weijie, Zeng, Yanqin, Zheng, Yunqiu, Cai, Bin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2023; Springer Nature B.V
• Subjects: AMP-activated protein kinase; Angiogenesis; Animal models; Apoptosis; Biomedical and Life Sciences; Biomedicine; Brain; Brain injury; Carotid arteries; Carotid artery; Cell activation; Cell Biology; Cell morphology; Cytology; Energy metabolism; Ischemia; Kinases; Metformin; Morphology; Neurobiology; Neuroprotection; Neurosciences; Original Research; Spatial discrimination learning; Spatial memory; Stenosis; Mice; Chronic cerebral ischemia (CCI); Metformin; AMP-activated protein kinase (AMPK); Gene knockout
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-022-01312-6

AMP-activated protein kinase (AMPK) is a regulator of cellular energy metabolism. Long-term use of metformin, an AMPK activator, was previously reported to be neuroprotective, as it promotes behavioral improvement and angiogenesis following an acute ischemic injury of the brain. However, only a few studies have demonstrated the role of AMPK in alleviating chronic cerebral ischemia (CCI) in mice models in the long-term (over 3 months). Therefore, we established a mouse model of CCI via bilateral carotid artery stenosis (BCAS) to explore the effect of AMPK on CCI. We used four groups of 3-month-old male C57BL/6 mice labeled as Sham, BCAS, BCAS + metformin treatment (BCAS + Met) and BCAS + AMPKα2 gene knockout (BCAS + KO). Three months after BCAS, we measured the AMPK protein expression, spatial learning and memory, Nissl bodies, cell apoptosis, astrocyte activation, and oligodendrocyte maturation. Additionally, we observed the brain tissues for changes in cell morphology. We observed that mice in the BCAS group had impaired spatial learning and memory compared with those in the sham group. The brain tissues of mice with CCI injury showed altered cell morphology, fewer Nissl bodies, cerebral cells apoptosis, and astrocyte activation. Interestingly, compared with mice from the BCAS group, the brains of mice from BCAS + Met group suffered lesser damage, whereas those of mice from the BCAS + KO group suffered more damage. The activation of AMPK, especially AMPKα2, plays a neuroprotective role during CCI in a mouse model of BCAS.