Heme oxygenase (HO) and
biliverdin reductase (BVR) activities are important for neuronal function and redox homeostasis.
Resuscitation from
cardiac arrest (CA) frequently results in neuronal injury and delayed neurodegeneration that typically affect vulnerable brain regions, primarily hippocampus (Hc) and motor cortex (mC), but occasionally also striatum and cerebellum. We questioned whether these delayed effects are associated with changes of the HO/BVR system. We therefore analyzed the activities of HO and BVR in the brain regions Hc, mC, striatum and cerebellum of rats subjected to
ventricular fibrillation CA (6 min or 8 min) after 2 weeks following
resuscitation, or
sham operation. From all investigated regions, only Hc and mC showed significantly decreased HO activities, while BVR activity was not affected. In order to find an explanation for the changed HO activity, we analyzed
protein abundance and
mRNA expression levels of HO-1, the inducible, and HO-2, the constitutively expressed
isoform, in the affected regions. In both regions we found a tendency for a decreased immunoreactivity of HO-2 using immunoblots and immunohistochemistry. Additionally, we investigated the histological appearance and the expression of markers indicative for activation of microglia [
tumor necrosis factor receptor type I (
TNFR1)
mRNA and immunoreactivity for ionized
calcium-binding adapter molecule 1 (Iba1])], and activation of astrocytes [immunoreactivity for
glial fibrillary acidic protein (GFAP)] in Hc and mC. Morphological changes were detected only in Hc displaying loss of neurons in the cornu ammonis 1 (CA1) region, which was most pronounced in the 8 min CA group. In this region also markers indicating
inflammation and activation of pro-death pathways (expression of HO-1 and
TNFR1 mRNA, as well as Iba1 and GFAP immunoreactivity) were upregulated. Since HO products are relevant for maintaining neuronal function, our data suggest that neurodegenerative processes following CA may be associated with a decreased capacity to convert
heme into HO products in particularly vulnerable brain regions.