minocycline and Leukemic-Infiltration

Previous studies in a mouse model of neonatal excitotoxic brain damage mimicking the brain lesions in human cerebral palsy showed microglial activation within 24 h after intracerebral injection of the glutamatergic analog ibotenate. Using this model, we studied the expression of CD-45 antigen, a marker of blood-derived cells, by these activated microglial cells labeled by Griffonia simplicifolia I isolectin B4. Immunohistochemistry performed during early development of excitotoxic lesions showed that most cells labeled with the isolectin B4 were CD-45-negative, suggesting that these early activated microglial cells were deriving chiefly from resident microglia and not from circulating monocytes. We also directly tested the hypothesis that activated resident microglia and/or blood-derived monocytes play a role in the pathophysiology of excitotoxic brain damage. Repeated i.p. administrations of chloroquine, chloroquine+colchicine, minocycline, or an anti-MAC1 antibody coupled to the toxin saporin before and/or after ibotenate injection induced a significant reduction in the density of isolectin B4-positive cells. This inhibition of resident microglial and/or blood-derived monocytes activation was accompanied by a significant reduction in the severity of ibotenate-induced brain lesions (up to 79% lesion size reduction with the highest minocycline dose) as well as of ibotenate-induced cortical caspase-3 activation (49% reduction).

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Antirheumatic Agents; Brain; Brain Injuries; Cell Count; Cell Death; Cerebral Cortex; Cerebral Palsy; Chloroquine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Glycoproteins; Ibotenic Acid; Immunohistochemistry; Lectins; Leukemic Infiltration; Leukocyte Common Antigens; Macrophage-1 Antigen; Mice; Microglia; Minocycline; Neurons; Neuroprotective Agents; Proliferating Cell Nuclear Antigen; Staining and Labeling; Time Factors