@article {Lalancette-H{\'e}bert2596, author = {M{\'e}lanie Lalancette-H{\'e}bert and Genevi{\`e}ve Gowing and Alain Simard and Yuan Cheng Weng and Jasna Kriz}, title = {Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain}, volume = {27}, number = {10}, pages = {2596--2605}, year = {2007}, doi = {10.1523/JNEUROSCI.5360-06.2007}, publisher = {Society for Neuroscience}, abstract = {Here we report in vivo evidence of a neuroprotective role of proliferating microglial cells in cerebral ischemia. Using transgenic mice expressing a mutant thymidine kinase form of herpes simplex virus driven by myeloid-specific CD11b promoter and ganciclovir treatment as a tool, we selectively ablated proliferating (Mac-2 positive) microglia after transient middle cerebral artery occlusion. The series of experiments using green fluorescent protein-chimeric mice demonstrated that within the first 72 h after ischemic injury, the Mac-2 marker [unlike Iba1 (ionized calcium-binding adapter molecule 1)] was preferentially expressed by the resident microglia. Selective ablation of proliferating resident microglia was associated with a marked alteration in the temporal dynamics of proinflammatory cytokine expression, a significant increase in the size of infarction associated with a 2.7-fold increase in the number of apoptotic cells, predominantly neurons, and a 1.8-fold decrease in the levels of IGF-1. A double-immunofluorescence analysis revealed a \~{}100\% colocalization between IGF-1 positive cells and Mac-2, a marker of activated/proliferating resident microglia. Conversely, stimulation of microglial proliferation after cerebral ischemia by M-CSF (macrophage colony stimulating factor) resulted in a 1.9-fold increase in IGF-1 levels and a significant increase of Mac2+cells. Our findings suggest that a postischemic proliferation of the resident microglial cells may serve as an important modulator of a brain inflammatory response. More importantly, our results revealed a marked neuroprotective potential of proliferating microglia serving as an endogenous pool of neurotrophic molecules such as IGF-1, which may open new therapeutic avenues in the treatment of stroke and other neurological disorders.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/27/10/2596}, eprint = {https://www.jneurosci.org/content/27/10/2596.full.pdf}, journal = {Journal of Neuroscience} }