White Matter Damage and Inflammation in Rat Models of Ischemic and Hemorrhagic Stroke

Cerebral ischemia and intracerebral hemorrhage (ICH) are both characterized by a prolonged inflammatory response and secondary injury phase, yet the spatial/temporal relationships between inflammation and white matter (WM) damage were largely unknown. Thus, I quantified the development of WM damage and inflammation over 7 days after ischemia, and 14 days after ICH. Following ischemia, myelin and axons were progressively damaged, and myelin damage coincided with neutrophil infiltration. Activated microglia/macrophages increased dramatically in the lesion core and edge, and selectively infiltrated damaged WM tracts while surrounding undamaged ones. To investigate the involvement of neutrophils in WM damage and inflammation after ICH, rats were rendered neutropenic before performing ICH. Neutrophil depletion reduced peri-hematomal axonal damage, BBB breakdown, and MMP-9 production at early times, and lessened microglia/macrophage and astrocyte responses at later times. Activated microglia/macrophages infiltrated peri-hematomal WM tracts, correlating with myelin fragmentation and axonal loss, and this was reduced with neutrophil depletion.MAS