Cold-Induced Spreading Depolarization in Rodent Brain Slices
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Authors
Kiarie, Edwin
Date
Type
thesis
Language
eng
Keyword
stroke , SPREADING DEPOLARIZATION , RODENT , BRAIN SLICES , Na+ /K+ pump , acute hippocampal slices
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Abstract
Early recognition of cold injury upon the ionic integrity of neurons came from non-hibernating mammals showing that deep hypothermia (<15°C) caused massive brain swelling, with intracellular accumulation of Na+ and cellular K+ depletion in brain parenchyma. This ‘cold swelling’ of brain tissue results from a mismatch between active and passive membrane transport processes. However, spreading depolarization (SD), a failure of the Na+/K+ pump, was not then considered a factor in the swelling. In a thesis by Donovan in the Andrew lab, we found that rat coronal slices chilled from 35 to 4.7ºC generated SD in the rat neocortex, not unlike brains from locust and fruit fly. Here we better characterize this phenomenon in rodent slices under more accurate temperature monitoring. A temperature ramp decreasing from 22 to 3ºC over 5 to 10 minutes induced cold SD, initiating focally in a coronal rodent brain slice with other foci developing as the slice was held at ~5ºC. This helps explain earlier microscopical work showing that cooling of organotypic hippocampal slices or of acute hippocampal slices during their preparation induces neuronal cell body swelling and dendritic beading in mouse neurons cooled to near 4ºC. In support, the current study shows this temperature elicits a classic SD event with typical neuron swelling (increased LT) and light scattering (decreased LT) associated with beading of dendrites during and immediately post-SD. This is presumably followed by a gradual recovery in aCSF at warmer physiological temperatures, forming the basis of innumerable acute slice preparation studies. We conclude that any brain slice from rodents cooled to < 4ºC likely undergoes `cold SD` in the gray matter of neocortex, striatum, and the hippocampal formation. This energy to drive SD is apparently maintained even within very cold mammalian gray matter because the Gibbs-Donnan equilibrium remains intact by Na+/K+ -ATPase transport. The pump maintains the still formidable chemical and electrical energy differential between the intra- and extracellular compartments. So while heat is lost from the tissue by lowering the ambient temperature, SD is generated so long as the pump continues functioning. When it fails, cold SD results as documented in insects. Likely explanations of pump failure is hypothermia lowering ATP production and the pump`s inability to shuttle cations across the cooled, viscous membrane.
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Attribution-NonCommercial-ShareAlike 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-ShareAlike 3.0 United States