Stress response to hypoxia in gerbil brain: HO-1 and MnSOD expression and glial activation

Hypoxic preconditioning has been shown to induce neuroprotection against a subsequent damaging insult. In order to study the underlying molecular and cellular mechanisms of hypoxic preconditioning, we investigated, in gerbil hippocampus, the effects in vivo of transient exposure to hypoxia (4% O-2 f or 6 min followed by either 48 h or 7 days of reoxygenation) (i) on the ind uction of 72 kDa heat shock protein (HSP72), heme oxygenase-l (HO-I) and ma nganese superoxide dismutase (Mn SOD) as assessed by Western immunoblotting and () on the astroglial and microglial activation as detected by both imm unohistochemistry and Western immunoblotting for GFAP, and histochemistry f or isolectin B4, respectively. Our data show that, although hypoxia and sub sequent reoxygenation led to neither neuronal damage nor HSP72 induction in gerbil hippocampus, it induced a progressive and sustained expression of H O-l and Mn SOD. As expected from the absence of neuronal death, hypoxia was not associated with microglial activation but led to a significant astrocy tic activation. These findings demonstrate that transient hypoxia enhances the antioxidative enzymatic defenses of the brain, which are susceptible to increased tolerance against a subsequent damaging insult. (C) 2001 Elsevie r Science B.V. All rights reserved.