Combined use of a cytoprotectant and rehabilitation therapy after severe intracerebral hemorrhage in rats

After moderate intracerebral hemorrhage (ICH), both hypothermia (HYPO) and constraint-induced movement therapy (CIMT) improve recovery and reduce the volume of brain injury. We tested the hypothesis that more severe ICH requires both cytoprotection and rehabilitation to significantly improve recovery. Rats were subjected to a unilateral striatal ICH via collagenase infusion. Rats remained normothermic or were subjected to mild HYPO (∼2 days) starting 12 h later. Fourteen days after ICH, half of the rats received CIMT (7 days of restraint of the less affected limb plus daily exercises); the remainder were untreated. Walking, limb use and skilled reaching were assessed up to 60 days, at which time animals were euthanized and the volume of tissue lost was determined. The HYPO treatment alone did not improve outcome, whereas CIMT alone provided significant benefit on the limb use asymmetry test. In the staircase test, the greatest benefit was achieved with the combination of HYPO and CIMT treatments. The volume of tissue lost after ICH was similar among groups arguing against cytoprotection as a mechanism of functional recovery. Finally, these findings suggest that, at least under the present circumstances (e.g., severe striatal ICH), CIMT provides superior benefit to HYPO and that combination therapy will sometimes further improve recovery.