• Y Gong, H Tian, G Xi, R F Keep, J T Hoff, and Y Hua.
• Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109-0532, USA.
• Acta Neurochir. Suppl. 2006 Jan 1;96:232-6.

AbstractHemoglobin degradation products result in brain injury after intracerebral hemorrhage (ICH). Recent studies found that intracerebral infusion of heme oxygenase inhibitors reduces hemoglobin- and ICH-induced brain edema in rats and pigs. The present study examined whether systemic use of zinc protoporphyrin (ZnPP), a heme oxygenase inhibitor, can attenuate brain edema, behavioral deficits, and brain atrophy following ICH. All rats had intracerebral infusion of 100-microL autologous blood. ZnPP (1 nmol/hour/rat) or vehicle was given immediately or 6 hours following ICH. ZnPP was delivered intraperitoneally up to 14 days through an osmotic mini-pump. Rats were killed at day 3 and day 28 after ICH for brain edema and brain atrophy measurements, respectively. Behavioral tests were performed. We found that ZnPP attenuated brain edema in animals sacrificed 3 days after ICH (p < 0.05). ZnPP also reduced ICH-induced caudate atrophy (p < 0.05) and ventricular enlargement (p < 0.05). In addition, ZnPP given immediately or 6 hours after ICH improved neurological deficits (p < 0.05). In conclusion, systemic zinc protoporphyrin treatment started at 0 or 6 hours after ICH reduced brain edema, neurological deficits, and brain atrophy after ICH. These results indicate that heme oxygenase may be a new target for ICH therapeutics.

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