Patients with
intracerebral hemorrhage (ICH) are at increased risk for major ischemic cardiovascular and cerebrovascular events. However, the use of preventative antithrombotic
therapy can increase the risk of ICH recurrence and worsen ICH-related outcomes.
Colchicine, an
anti-inflammatory agent, has the potential to mitigate
inflammation-related
atherothrombosis and reduce the risk of ischemic vascular events. Here we investigated the safety and efficacy of
colchicine when used both before and acutely after ICH. We predicted that daily
colchicine administration would not impact our safety measures but would reduce
brain injury and improve functional outcomes associated with
inflammation reduction. To test this, 0.05 mg/kg
colchicine was given orally once daily to rats either before or after they were given a
collagenase-induced striatal ICH. We assessed neurological impairments, intra-parenchymal
bleeding, Perls positive cells, and
brain injury to gauge the therapeutic impact of
colchicine on
brain injury.
Colchicine did not significantly affect
bleeding (average = 40.7 μL) at 48 hrs, lesion volume (average = 24.5 mm3) at 14 days, or functional outcome (median neurological deficit scale score at 2 days post-ICH = 4, i.e., modest deficits) from 1-14 days after ICH.
Colchicine reduced the volume of Perls positive cells in the perihematomal zone, indicating a reduction in
inflammation. Safety measures (body weight, food consumption, water consumption, hydration, body temperature, activity, and
pain) were not affected by
colchicine. Although
colchicine did not confer neuroprotection or functional benefit, it was able to reduce perihematomal
inflammation after ICH without increasing
bleeding. Thus, our findings suggest that
colchicine treatment is safe, unlikely to worsen
bleeding, and is unlikely but may reduce secondary injury after an ICH if initiated early post ICH to reduce the risk of ischemic vascular events. These results are informative for the ongoing CoVasc-ICH phase II randomized trial (NCT05159219).