Differential Roles of Neuro-Inflammatory Regulator, MAPK11 in Cortex and Hippocampus Following Post-Stroke Cognitive...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Ischaemic stroke is a primary cause of long-term cognitive deficits, particularly impacting memory and learning.
• The hippocampus and cortex are vital for cognitive functions affected by stroke, but region-specific responses to ischaemic damage, especially inflammation, are understudied.
• Understanding these region-specific mechanisms is crucial for developing targeted therapies for post-stroke cognitive impairment.

Purpose of the Study:

• To investigate the region-specific neural, molecular, and cellular mechanisms underlying cognitive impairments after ischaemic stroke.
• To identify key genes and pathways involved in inflammation-mediated neurodegeneration in the cortex and hippocampus.
• To explore the therapeutic potential of targeting specific molecular pathways for mitigating cognitive deficits.

Main Methods:

• Development of a bilateral common carotid artery occlusion (BCCAo) model in rats to induce ischaemic stroke.
• Neurobehavioral assessments to evaluate memory and learning deficits post-stroke.
• Next-generation sequencing (NGS) and in-depth network analysis of isolated cortical and hippocampal tissues.
• Analysis of gene expression, including MAP2K6, MAPK11, and upstream Akt/GSK3β pathway components.

Main Results:

• Identification of 13 significant neurodegenerative hub genes, including Map2k6 and Mapk11, crucial in inflammation-mediated cascades.
• Significant upregulation of MAP2K6/MAPK11 observed in the cortex of ischaemia-treated rats.
• Comparative analysis revealed diminished MAPK11 expression in the hippocampus, suggesting region-specific responses.
• Demonstrated MAPK11's role as a neuroinflammatory regulator, with potential to alleviate cognitive impairments via the Akt/GSK3β pathway.

Conclusions:

• MAP2K6/MAPK11 play significant roles in driving neuroinflammatory processes that regulate ischaemic cascades.
• The hippocampus exhibits relative resilience in preserving cognitive function compared to the cortex post-ischaemia.
• Targeting MAPK11 and associated neuroinflammatory pathways in the cortex presents a promising therapeutic strategy for post-stroke cognitive impairment (PSCI) in chronic ischaemia.