Characterization of microglial reaction after middle cerebral artery occlusion in rat brain

Abstract

We have studied the microglial reaction that accompanies cortical infarction induced by middle cerebral artery occlusion (MCAO). Lectin histochemistry with the B4-isolectin from Griffonia simplicifolia as well as immunocytochemistry with a panel of monoclonal antibodies directed against major histocompatibility complex (MHC) and lymphocytic antigens were performed. Principal attention was focused on neocortical and thalamic regions, representative of primary and secondary ischemic damage, respectively. With the lectin procedure, activated microglial cells were abundant in the neocortex 24 hours after MCAO. In contrast, microglial activation in the thalamus was not apparent until day 2 after MCAO. On day 5, MHC class II antigen was expressed by reactive microglia in fiber tracts traversing the striatum, but was absent from activated microglia in the primary cortical infarction area. MHC class I and lymphocytic antigens were expressed differentially on microglia with class I antigens appearing early and lymphocytic antigens appearing late in the time course after focal ischemia. The findings are compatible with previous studies during global ischemia and confirm the early activation and the progressive nature of immunomolecule expression on activated microglia after an ischemic insult. In addition to neocortical and thalamic sites, our results showed an early microglial activation to be present also in forebrain regions outside of the middle cerebral artery (MCA) territory, such as the contralateral cortex and hippocampus. A unilateral microglial reaction was also detectable after long-term survival (> or = 4 weeks) in the pyramidal tracts, as well as in the corticospinal tracts at cervical but not lumbar spinal cord levels. Ischemia-induced neuronal damage, as evaluated by Nissl staining, was found only in cortical and thalamic regions. We conclude that the demonstration of reactive microglia indicates not only imminent ischemic neuronal damage within MCA territory but can also delineate extra-focal disturbances, possibly reflecting subtle and transitory changes in neuronal activity.

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

“…Microglia are activated following ischemic brain injury (Morioka et al, 1993) and excitotoxic brain lesions (Topper et al, 1993). We observed an increase in neurosphere proliferation using tissue harvested 1-2 weeks following ischemic and excitotoxic brain lesions.…”

Transplantation of Human Placenta-Derived Multipotent Stem Cells Reduces Ischemic Brain Injury in Adult Rats

“…Acute ischemic brain injury induces cytotoxic edema (cell swelling), inflammation, and cell infiltration lasting from hours to days (25,32). Cytotoxic edema causes a decrease in extracellular volume and results in restriction of microscopic water molecular diffusion (29).…”

“…Stroke-induced inflammation can extend for days after injury (25). It is thus likely that treatment aiming at inflammatory therapy may have relatively long-lasting therapeutic effects.…”

Interleukin‐13 and ‐4 induce death of activated microglia

“…Axotomy of facial nerves leads to microglial proliferation in the regenerating facial motor nucleus (Raivich et al, 1991) and migration of these cells into damaged regions from adjacent intact areas (Jensen et al, 1994). In brain ischemia due to middle cerebral artery occlusion, microglia become abundant in the infarct area within 24 h (Morioka et al, 1993). Traumatic injury also stimulates proliferation of microglia (Giulian et al, 1991).…”