Granulocyte-colony stimulating factor promotes brain repair following traumatic brain injury by recruitment of microglia and increasing neurotrophic factor expression.

摘要: Purpose The overall objective was to elucidate cellular mechanisms by which G-CSF enhances recovery from traumatic brain injury in a hippocampal-dependent learning task. Methods Chimeric mice were prepared transplanting bone marrow cells that express green fluorescent protein (GFP+) transgenic "green" into C57BL/6 mice. Two months later, the animals sustained mild controlled cortical impact (CCI) right frontal-parietal cortex, followed (100 μg/kg) treatment for 3 consecutive days. primary behavioral end-point performance on radial arm water maze (RAWM) assessed before and after CCI (days 7 14). Secondary endpoints included a), motor rotating cylinder (rotarod), b) measurement of microglial astroglial response, c) hippocampal neurogenesis, d) measures neurotrophic factors (BDNF, GDNF) homogenates. Results resulted significantly better rotorod at one week, RAWM two weeks. changes found 2 wks group increased numbers newborn neurons as well astrocytosis microgliosis striatum frontal cortex both sides brain. GFP+ co-labeled with Iba1 (microglial marker) comprised significant proportion striatal microglia treated animals, indicating capacity increase recruitment site injury. Neurotrophic GDNF BDNF, elaborated activated astrocytes, Conclusions serves factor increases neurogenesis (or survival new-born neurons), activates astrocytes microglia. In turn, these glia release plethora cytokines contribute, poorly understood cascade, brain's repair response. also acts directly marrow-derived enhance circulating monocytes CCI.