Differential Expression of the Immediate Early Genes c-Fos, c-Jun, JunB, andNGFI-B in the Rat Brain following Transient Forebrain Ischemia

Abstract

The temporospatial expression pattern of four immediate early genes (IEGs) (c-fos, c-jun, junB, NGFI-B) following 30 min of global ischemia was investigated in rat brains by in situ hybridization and immunohistochemistry (c-fos). All examined IEG mRNAs, as well as Fos-like immunoreactivity, increased transiently in vulnerable and resistant brain regions following ischemia, but the induction profiles were distinct. Ischemia caused a post-ischemic early-onset, transient c-fos induction in wide-spread regions, as well as a late-onset induction restricted to vulnerable regions. Late-onset c-fos induction was observed in the CA1 region and the ventral thalamus but not in the striatum or neocortex, where neurons degenerate at a quicker pace. After recirculation, c-jun mRNA appeared to be initially coinduced with c-fos mRNA, but c-jun mRNA levels remained elevated or increased in various regions, including all vulnerable regions, when c-fos mRNA had already declined to near basal levels. Compared to c-fos and c-jun, junB induction was less pronounced and confined largely to the dentate gyrus. NGFI-B mRNA increased moderately and only in brain regions exhibiting the most dramatic c-fos increases and with similar kinetics. The differential activation of the investigated IEGs suggests that rather complex long-term adaptive processes may be initiated at the genomic level after global ischemia. The present findings provide further evidence that the activation of IEGs forms part of the brain's metabolic response to ischemia, but no simple correlation appears to exist between the induction of the investigated IEGs and the phenomenon of selective vulnerability.

Changes of Endogenous Antioxidant Enzymes during Ischemic Tolerance Acquisition

“…The most noticeable difference in comparison to SOD is that CAT reaches peak of its postischemic activity 24 h after ischemia. This fact is another demonstration of differential expression of proteins in individual time intervals after ischemia (21,36).…”

A Reproducible Model of Middle Cerebral Artery Occlusion in Mice: Hemodynamic, Biochemical, and Magnetic Resonance Imaging

“…Ischemia induces numerous genes such as the immediate-early genes c-fos, c-jun, and junB Kiessling and Gass, 1994;Kinou chi et al, 1994;Neumann et al, 1994) and genes encod ing the heat shock protein hsp72 (Kinouchi et al, 1993;Nowak and Jacewicz, 1994;Massa et al, 1996) and the cytokines interleukin-l, interleukin-6, and tumor necro sis factor-a (Wiessner et al, 1993;Buttini et al, 1996). The main interest in investigating ischemia-induced ge nomic responses in the brain is to clarify the mechanisms of inherent degenerative or protective processes and to define targets for specific modulations of these cellular hours after MCA occlusion, imaging of ATP, tissue pH, and cerebral protein synthesis allowed differentiation between the central infarct core, in which ATP was depleted, and a periph eral penumbra with reduced protein synthesis and tissue acido sis but preserved ATP content Perfusion deficits and ischemic tissue alterations could also be detected by perfusion-and dif fusion-weighted magnetic resonance imaging, demonstrating the feasibility of dynamic evaluations of infarct evolution, The use of multiparametric imaging techniques in this improved MCA occlusion model opens the way for advanced pathophysi ological studies of stroke in gene-manipulated animals, Key Words: Cerebral ischemia-Mouse-Middle cerebral artery occlusion-Magnetic resonance imaging, responses.…”

Maturation Phenomenon in Cerebral Ischemia IV

“…a-; fields are not shown here). On the other-hand, adult rats subjected to four-vessel occasion showed the highest level of c-fos mRNA in CM at 3 h of recovery, with SZen decUne and return to basal level at 12-24 h [24]. This discrepancy is mosXly due to differences in the ischemic models.…”

“…[18]. Cerebral ischemia is also a well-known stimulator of c-fos, which has been demonstrated in animals subjected to either focal or global arrest of blood flow to the brain [15,24]. The ischemic induction of c-fos mRNA was demonstrated in both vulnerable and resistant regions and its localization depended on the model of ischemia.…”