M. Jake Pushie, Nicole J. Sylvain, Huishu Hou, Dominic George and Michael E. Kelly*,
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引用次数: 0
Abstract
Element dysregulation is a pathophysiologic hallmark of ischemic stroke. Prior characterization of post-stroke element dysregulation in the photothrombotic model demonstrated significant element changes for ions that are essential for the function of the neurovascular unit. To characterize the dynamic changes during the early hyperacute phase (<6 h), we employed a temporary large-vessel occlusion stroke model. The middle cerebral artery was temporarily occluded for 30 min in male C57BL/6 mice, and coronal brain sections were prepared for histology and X-ray fluorescence microscopy from 5 to 120 min post-reperfusion. Ion dysregulation was already apparent by 5 min post-reperfusion, evidenced by reduced total potassium in the lesion. Later time points showed further dysregulation of phosphorus, calcium, copper, and zinc. By 60 min post-reperfusion, the central portion of the lesion showed pronounced element dysregulation and could be differentiated from a surrounding region of moderate dysregulation. Despite reperfusion, the lesion continued to expand dynamically with increasing severity of element dysregulation throughout the time course. Given that the earliest time point investigated already demonstrated signs of ion disruption, we anticipate such changes may be detectable even earlier. The profound ion dysregulation at the tissue level after reperfusion may contribute to hindering treatments aimed at functional recovery of the neurovascular unit.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research