Interpretation of Intrinsic Optical Signals and Calcein Fluorescence during Acute Excitotoxic Insult in the Hippocampal Slice
Abstract
Immediate (acute) neuronal damage in response to overstimulation of glutamate receptors results from toxic exposure to food poisons acting as glutamate analogues. Glutamate agonist application evokes dramatic intrinsic optical signals (IOSs) in the rat hippocampal slice preparation, particularly in the CA1 region. Theoretically IOSs are generated by alterations to neuronal and glial structure that change light transmittance (LT) in live brain tissue. To better understand such signals, IOSs evoked by the glutamate agonist N-methyl-D-aspartate were imaged in the rat hippocampal slice. We correlated these excitotoxic signals with: (1) biophysical principles governing light transport, (2) tissue volume changes as measured using a free intracellular fluorophore (calcein), (3) dendritic morphology visualized by dye injection, and (4) standard histopathology. In theory LT elevation evoked during acute excitotoxic swelling is generated by change to subcellular structure that reduces light scattering during cell swelling. However, in responsive dendritic regions, initial LT elevation caused by cell swelling was overridden by the formation of dendritic beads, a conformation that increased light scattering (thereby reducing LT) even as the calcein signal demonstrated that the tissue continued to swell. Thus IOS imaging reveals acute somatic and dendritic damage during excitotoxic stress that can be monitored across slices of brain tissue in real time.
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A similar morphology to severe ischemia in vivo has been observed with brain slices during glutamate-induced excitotoxicity.
“A similar morphology has been observed with brain slices during glutamate-induced excitotoxicity (Jarvis et al., 1999).”
From Rapid Reversible Changes in Dendritic Spine Structure<i>In Vivo</i>Gated by the Degree of Ischemia (2005) · cites this paper as Jarvis et al., 1999
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Gutwein, A. B. (2013) · Journal of Bioresource Management
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Aiba, I. (2012) · UNM’s Digital Repository (University of New Mexico)
- Authors
- Jarvis, C. R., Lilge, L., Vipond, G. J., & Andrew, R. D.
- Affiliations
- Queen's University (CA)
- University of Toronto (CA)
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 10
- Issue
- 4
- Pages
- 357-372
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2075350214
- Cited by
- 58
- References
- 58
- Citations by year
- 2022: 1 · 2021: 1 · 2017: 5 · 2016: 1 · 2015: 4 · 2013: 2 · 2012: 6
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- intrinsic optical signals, excitotoxicity, NMDA, glutamate receptor agonists, hippocampal slices, CA1 region, calcein fluorescence, optical transmittance, light scattering, neuronal swelling, dendritic morphology, glutamate analogues
- MeSH terms
- Animals, Fluoresceins, Fluorescent Dyes, Furosemide, Hippocampus, Image Processing, Computer-Assisted, Male, Microscopy, Fluorescence, Neurons, Neurotoxins, N-Methylaspartate, Rats, Sprague-Dawley, Pyramidal Cells, Rats, In Vitro Techniques
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