Neural Cytoskeleton Modulation after Transient Ischemic Attack and Region-Specific Brain Metabolism Insights
Transient ischemic attack (TIA) is a symptomatic diagnosis disease characterized as reversible ischemic stroke-like neurological deficit. One-third of the TIA patients have recurrent episodes, and TIA presents as a high vascular risk factor for severe stroke, mild cognitive impairment, and dementia. However, the neuropathophysiology of TIA has been less studied. Here, we established recurrent TIA model in rats with no neurological deficits and no/minimal apoptosis cells detected. Our study demonstrated that recurrent TIA induces neuronal cytoskeleton modification, astrogliosis and microgliosis in the TIAaffected cortical and basal ganglia regions, as well as in the white matter in terms of corpus callosum in the acute and subacute stage. Our data indicate recurrent TIA-induced neuronal cytoskeletal modification and neuroinflammation, may be potentially involved in the vascular contribution to cognitive impairment and dementia. Even though neurological deficits are transient in TIA patients, the brain presents morphologic and metabolic change in response to transient ischemic insult. This can be reflected on the remodeling of cytoskeleton, which plays a critical role in the mitochondria shape and motility maintenance. In addition, the interaction between cytoskeletal components and mitochondria is highly involved in the oxidative phosphorylation and mitochondrial respiration regulation. To investigate the brain metabolic signatures in the normal and pathological conditions, our study optimized a method that enables metabolic function assessment of anatomically defined brain structures by the Seahorse XFe96 analyzer in rodents. Our data demonstrated that the rodent brain has region-specific glucose metabolic profile, the cerebellum displays a more quiescent phenotype than cerebral cortex, basal ganglia, and hippocampus. Additionally, the rodent brain has relatively low mitochondrial oxidative phosphorylation efficiency with high proton leaklinked respiration. Through our proof-of-principle study, we expect to acquire critical insights that will enable future research in pursuit of spatial mapping of the brain glucose metabolism in physiological and pathological conditions (e.g., TIA condition), and further explore the mechanisms and significance of mitochondrial uncoupling of the brain.