Is Fos Protein Expressed by Dying Striatal Neurons after Immature Hypoxic–Ischemic Brain Injury?

Abstract

The transient induction of mRNA for the immediate–early gene c-fos has been reported following hypoxic–ischemic brain injury in the immature brain. However, no studies have examined the temporal expression of Fos protein, which is the functionally relevant product of c-fos gene expression. Increased expression of Fos protein has been linked to cell death. We therefore examined whether Fos protein is expressed by dying neurons after immature hypoxic–ischemic brain injury. A well characterized immature rat model of hypoxic–ischemic injury at postnatal day (PN) 7 was used. Three hypoxic–ischemic and three normoxic control pups were studied per time point (i.e., 0, 2, 12, 24, 48, and 72 h posttreatment). Expression of Fos within striatal and other neurons was detected immunocytochemically. Fos protein was expressed within dying striatal neurons at 0–12 h after hypoxia–ischemia. However, detection was only seen in 2 of 17 hypoxic–ischemic pups. These 2 pups had ≥80% of their striatal neurons dying within their right, hypoxic–ischemic-exposed hemisphere. Fos protein expression after severe injury may, therefore, be a response to extraordinary or extreme stress. The absence of Fos protein expression in the majority of hypoxic-ischemic pups, which all exhibited striatal neuronal death, suggests that Fos expression is not necessary for cell death to occur. Therapies directed against Fos protein expression may therefore have limited usefulness in immature hypoxic–ischemic brain injury.