Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats.

BACKGROUND AND PURPOSE: Both hypothermia and decompressive craniectomy (DC) have been shown to reduce ischemic injury in experimental middle cerebral artery (MCA) infarction. This study was designed to evaluate the effect of combined DC and hypothermia on infarction size and neurological outcome in a rat model of MCA occlusion (MCAO). METHODS: MCAO was performed in 72 Wistar rats assigned to groups A through F. In group A, mild hypothermia (32 degrees C) was induced 1 hour after MCAO for 5 hours; normothermia was maintained in group B. After 6 hours of survival, infarction size was calculated for animals of groups A and B. In group C, DC alone was performed 4 hours after MCAO; hypothermia without DC was performed 1 hour after MCAO and maintained for 5 hours in group D. Combined DC and hypothermia were performed in group E. No therapy was performed in group F (control). Infarction size and neurological performance after 24 hours were used as study end points (groups C through F). RESULTS: Permanent postischemic hypothermia significantly reduced infarction size 6 hours after MCAO compared with controls (group A, 6.6+/-2.4%; group B, 20.2+/-2.6%; P<0.01). Twenty-four hours after MCAO, infarction size was not significantly reduced by hypothermia alone (group D, 21.9+/-3.6%). Compared with controls (group F, 23.3+/-3.3%), infarction size was significantly reduced and neurological performance was significantly improved in animals treated by DC (group C, 11.8+/-3.4; P<0.001). Combined hypothermia and DC resulted in additional reduction of infarction size (group E, 9.1+/-2.4%) and improved neurological score (P<0.01). CONCLUSIONS: Early DC significantly reduces infarction size and improves neurological outcome in MCA infarction in rats. Temporary mild hypothermia delays infarct evolution but does not significantly reduce definite infarction size or improve neurological outcome. Combined hypothermia and DC yield significant additional benefit.

Delayed neuroprotective effect of insulin-like growth factor-i after experimental transient focal cerebral ischemia monitored with mri.

BACKGROUND AND PURPOSE: Insulin-like growth factor (IGF) treatment has been shown to have trophic and neuroprotective effects in vitro and in vivo in different lesion models. IGF-I has potent neuroprotective effects after hypoxic-ischemic injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only partially understood. Therefore, in the present study, we evaluated, by applying MRI monitoring, whether a clinically relevant systemic administration of IGF-I can achieve a long-lasting neuroprotective effect. METHODS: Male Wistar rats underwent transient occlusion of the right middle cerebral artery for 1 hour by using the suture occlusion model. Animals then were intraventricularly treated with 33.33 microg IGF-I/d for 3 days (group A, the IGF-I group [n=13]; group B, the placebo group [n=14]) or subcutaneously treated with 200 microg IGF-I/d for 7 days (group D, the IGF-I group [n=10]; group E, the placebo group [n=10]). Groups C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment was begun 30 minutes after occlusion of the middle cerebral artery. Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging, perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were weighed and neurologically assessed daily (rating scale ranged from 0, indicating no deficit, to 5, indicating death). On the third day (intraventricular trial) and on the seventh day (subcutaneous trial), animals were euthanized, and brain sections were stained with triphenyltetrazolium chloride. RESULTS: The mean infarct volume was 52.9+/-25.2 mm(3) in intraventricularly treated animals versus 146.4+/-62.2 mm(3) in control animals (P<0.01) and 42.2+/-17.9 mm(3) in subcutaneously IGF-I-treated animals versus 73.1+/-38.1 mm(3) in control animals (P<0.05). Apparent diffusion coefficient-derived lesion volume at 60 minutes after occlusion was 40.4+/-23.7 mm(3) versus 38.3+/-19.3 mm(3) (P=NS), increased to 168.3+/-49.55 mm(3) versus 105.5+/-33.8 mm(3) (P<0.05) at 24 hours, and then decreased to 55.8+/-30.3 mm(3) versus 23.3+/-20.2 mm(3) (P<0.05) for control and IGF-I-treated animals, respectively. The T2-weighted-derived ischemic lesion volume at 24 hours after occlusion was 236+/-49.2 mm(3) versus 115.9+/-56.8 mm(3) (P<0.05) and decreased to 115.9+/-26.2 mm(3) versus 75.7+/-35.8 mm(3) (P<0.05) at day 7 for control and IGF-I-treated animals, respectively. The relative regional cerebral blood volume was reduced to 50% before reperfusion in all regions of interest except for region of interest 1 (vessel territory of anterior cerebral artery), recovered during reperfusion, but was not different between the control and the growth factor-treated group at any imaging time point. There was no significant difference in weight loss. There was less neurological deficit after ischemia in intraventricularly and subcutaneously IGF-I-treated animals compared with control animals (P<0.05). CONCLUSIONS: Continuous treatment with intraventricularly and subcutaneously administered IGF-I achieved a long-lasting neuroprotective effect as early as 24 hours after ischemia as measured by MRI. Therefore, IGF-I may represent a new approach to the treatment of focal cerebral ischemia.