The Influence of Hypothermia on Outcome After Intracerebral Hemorrhage in Rats

Abstract

Background and Purpose— Late hypothermia (HYPO) reduces injury after collagenase-induced intracerebral hemorrhage (ICH), whereas early HYPO does not because it exacerbates the protracted bleeding that occurs in this model. We hypothesized that early HYPO would not increase bleeding after whole blood infusion and thus expected early HYPO to improve outcome through reducing secondary consequences of ICH (eg, inflammation). Methods— Autologous blood (100 μL) was infused into the striatum. Rats were maintained at normothermia or subjected to mild (33°C to 35°C) HYPO for 2 days starting 1 (HYPO-1) or 4 hours (HYPO-4) after ICH. Hematoma volume was measured at 12 hours to determine whether HYPO-1 aggravated bleeding. We measured blood–brain barrier (BBB) disruption and edema 2 days after ICH in all groups. At 4 days, we counted degenerating neurons, neutrophils, and iron-positive cells (eg, macrophages) in the lesioned hemisphere. Recovery was assessed using several behavioral tests (ie, staircase reaching task, ladder walking task, limb use cylinder test) over 7 or 30 days, at which time we quantified lesion volume. Results— HYPO did not increase bleeding. Both HYPO treatments reduced BBB disruption and infiltration of inflammatory cells. HYPO-1 treatment modestly reduced edema and provided limited to no functional benefit in the behavioral tests. HYPO did not affect lesion volume. Conclusions— HYPO reduced edema, BBB disruption, and inflammation. Although encouraging, HYPO treatment must be improved so that histological and functional benefit are obtained before clinical investigation. Otherwise clinical failure is anticipated.