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Ultrastructural changes of neuronal mitochondria after transient and permanent cerebral ischemia
Nina J Solenski1, Charles G diPierro, Patricia A Trimmer
1Department of Neurology, University of Virginia, Health Sciences System, Charlottesville 22908, USA. njs2j@virginia.edu
Background And Purpose:
Mitochondrial swelling is one of the most striking and initial ultrastructural changes after acute brain ischemia. The purpose of the present study was to examine the role of reperfusion of the cerebral cortex after transient focal cerebral ischemia on neuronal mitochondrial damage.
Methods:
Male Sprague-Dawley rats (n=16) were subjected to either temporary or permanent occlusion of the middle cerebral artery and bilateral carotid arteries. Three experimental conditions were compared: group I, permanent ischemia (3, 5, and 24 hours); group II, transient ischemia (2, 24 hours of reperfusion); and sham surgery. Anesthetized rats were killed by cardiac perfusion, and brain tissue was removed ipsilaterally and contralaterally from the ischemic core section of the frontoparietal cortex. Fixed tissue was prepared for electron microscopic examination, and electron microscopic thin sections of random neurons were photographed. Perinuclear neuronal mitochondria were analyzed in a blinded manner for qualitative ultrastructural changes (compared with sham control) by 2 independent investigators using an objective grading system.
Results:
Cortical neuronal mitochondria exposed to severe ischemic/reperfusion conditions demonstrated dramatic signs of injury in the form of condensation, increased matrix density, and deposits of electron-dense material followed by disintegration by 24 hours. In contrast, mitochondria exposed to an equivalent time of permanent ischemia demonstrated increasing loss of matrix density with pronounced swelling followed by retention of their shape by 24 hours.
Conclusions:
Neuronal mitochondria undergoing transient versus permanent ischemia exhibit significantly different patterns of injury. Structural damage to neuronal mitochondria of the neocortex occurs more acutely and to a greater extent during the reperfusion phase in comparison to ischemic conditions alone. Further research is in progress to delineate the role of oxygen free radical production in the observed mitochondrial damage during postischemic reoxygenation.
Insights
Reperfusion after brain ischemia causes acute mitochondrial damage in cortical neurons. Permanent ischemia leads to swelling, while reperfusion causes disintegration, indicating distinct injury patterns.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Acute brain ischemia triggers mitochondrial swelling as an initial ultrastructural change.
- Understanding neuronal mitochondrial response to reperfusion is crucial for acute ischemic stroke research.
Purpose of the Study:
- To investigate the impact of cerebral cortex reperfusion following transient focal cerebral ischemia on neuronal mitochondrial damage.
- To compare mitochondrial injury patterns between transient (ischemia/reperfusion) and permanent ischemia.
Main Methods:
- Rats underwent middle cerebral artery occlusion (MCAO) for permanent or transient ischemia.
- Brain tissue from ischemic and sham groups was analyzed using electron microscopy.
- Neuronal mitochondria were assessed for ultrastructural damage using a blinded grading system.
Main Results:
- Mitochondria under ischemia/reperfusion showed condensation, increased density, and disintegration by 24 hours.
- Mitochondria under permanent ischemia exhibited matrix density loss and swelling, retaining shape by 24 hours.
- Transient ischemia with reperfusion induced more acute and extensive mitochondrial damage than permanent ischemia.
Conclusions:
- Neuronal mitochondria display distinct injury patterns in transient versus permanent ischemia.
- Reperfusion exacerbates mitochondrial damage in the neocortex more than ischemia alone.
- Further studies are needed to explore the role of oxygen free radicals in postischemic mitochondrial damage.