Peri-hemorrhagic degeneration accompanies stereotaxic collagenase-mediated cortical hemorrhage in mouse

The cortex is a key brain region vulnerable to intracerebral hemorrhage (ICH) associated with stroke and head trauma. Animal models of ICH, via blood or collagenase infusion, have been developed most commonly to target the striatum. Here, we show that stereotaxic injection of collagenase type IV into two sites of the right cortex of adult C57BL6 mice produced hemorrhage to the cortex, subcortical white matter and hippocampus at day 1 post-injury, followed by cortical volume decrement by day 7. Reductions in MAP2- and NeuN-positive neurons were detected at day 1 and 7 post-injury in the core and peri-hemorrhagic cortex, respectively. Fluoro-Jade positive degenerating neurons were observed at day 1 in the peri-hemorrhagic area. An aberrant aggregation of GFAP-positive astrocytes and a significant reduction in RIP-positive oligodendroglial cells were detected at day 7 post-injury in the cortical area. In addition, a significant decrement in retrogradely Cholera Toxin Subunit B-labeled corticospinal neurons was recognized at day 14 post-injury in the ipsilateral cortex. Among the behavioral tests employed, the pole climb movement test robustly detected significant motor dysfunction at day 1, 3, and 7 post-injury that positively but inversely correlated with cortical volume at day 1 and 7 post-injury, respectively. The consistent observation of neuronal cell loss in the hemorrhagic core that subsequently extended to degeneration of neurons in the peri-hemorrhagic area, with accompanying motor abnormalities at least up to the subacute phase, advances this cortical hemorrhage model as a platform for examining the pathophysiology of and experimental treatments for ICH.