Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice

Abstract

We investigated the temporal course of microglia activation in different brain regions after permanent middle cerebral artery (MCA) occlusion in mice and compared this microglia response with the appearance of apoptotic cells, Microglia activation and morphological changes of microglial cells were visualized using an immunohistochemical method with a polyclonal antibody recognizing the mouse CR3 complement receptor. Cells showing morphological and biochemical features of apoptosis were identified using the terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) method and light microscopy. As early as 30 min after onset of MCA occlusion activated microglia with hypertrophic cell bodies and stout processes were detected in the periphery of the ischemic lesion as identified by diffusion-weighted magnetic resonance imaging. A wider distribution and a progressive increase in the number of activated microglia was found with increasing time. Only few TUNEL-positive cells with apoptotic features were observed within the lesion area at 6 h after onset of cerebral ischemia. From 12 h after MCA occlusion onward a tremendous increase in the number of TUNEL-positive cells was found. Within the thalamus from 24 h onward microglia cells with few processes, irregular morphology and fragmented appearance were detected. Microglia activation in the thalamus progressed up to 4 weeks after MCA occlusion, but had declined after 90 days. Neuronal degeneration in the thalamus as determined by anti-neuronal nuclei immunohistochemistry progressed from 6 days after MCA occlusion onward. Only a few TUNEL-positive cells were found in the thalamus. In summary, microglia activation both in the primary cortical lesion area and in the secondarily affected thalamus preceded the manifestation of tissue injury. These observations encourage further studies on the role of microglia in focal cerebral ischemia.

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model

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Physiology of Microglia

“…Findings derive from responses to injury (152,488,743), ischemia (778), or autoimmune challenges (722). Microglial activation may start with an early emergency response, such as defenseoriented functions, to fight off an infection or to limit further damage after an injury.…”

99m Tc Annexin V Imaging of Neonatal Hypoxic Brain Injury

“…9 However, the presence or absence of apoptosis with respect to diffusion-weighted MRI has been examined only in animals that suffered permanent ADC changes that directly corresponded to areas of infarction induced by transient but moderately severe ischemia. 2,13 Although changes in diffusion correlate with apoptosis, they are not a direct marker of the process. In 1998, a radiopharmaceutical approach to detect apoptosis in vivo was described.…”