Trauma‐induced alterations in cognition and Arc expression are reduced by previous exposure to ⁵⁶Fe irradiation

Abstract

Exposure to ionizing irradiation may affect brain functions directly, but may also change tissue sensitivity to a secondary insult such as trauma, stroke or degenerative disease. To determine if a low dose of particulate irradiation sensitizes the brain to a subsequent injury, C56BL6 mice were exposed to brain only irradiation with 0.5 Gy of 56Fe ions. Two months later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Three weeks after trauma animals received multiple BrdU injections and 30 days later were tested for cognitive performance in the Morris water maze. All animals where able to locate the visible and hidden platform during training; however, treatment effects were seen when spatial memory retention was assessed in the probe trial (no platform). While sham and irradiated animals showed spatial memory retention, mice that received trauma alone did not. When trauma was preceded by irradiation, performance in the water maze was not different from sham-treated animals, suggesting that low dose irradiation had a protective effect in the context of a subsequent traumatic injury. Measures of hippocampal neurogenesis showed that combined injury did not induce any changes greater that those seen after trauma or radiation alone. After trauma there was a significant decrease in the percentage of neurons expressing the behaviorally-induced immediate early gene Arc in both hemispheres, without associated neuronal loss. After combined injury there were no differences relative to sham-treated mice. Our results suggest that combined injury resulted in decreased alterations of our endpoints compared to trauma alone. While the underlying mechanisms are not yet known, these results resemble a preconditioning, adaptive, or inducible-like protective response, where a sublethal or potentially injurious stimulus (i.e. irradiation) induces tolerance to a subsequent and potentially more damaging insult (trauma).

miR21 is Associated with the Cognitive Improvement Following Voluntary Running Wheel Exercise in TBI Mice

“…Previous reports showed that miR21 levels in the hippocampus and cerebral cortex was up-regulated in TBI rodent, which suggested that the elevated miR21 might be involved in the intricate process of TBI course (Redell et al 2011;Rosi et al 2012). Additionally, others demonstrated that transgenic overexpression of miR21 in mice attenuated the beneficial hypertrophic response to spinal cord injury (SCI), whereas inhibition of miR21 augmented the astrocytic response after SCI (Bhalala et al 2012).…”

“…A mouse model of TBI was developed using a device that produces controlled cortical impact (CCI), permitting independent manipulation of tissue deformation and impact velocity. The left parietotemporal cortex was subjected to CCI [2 mm tissue deformation and 6.0 m/s (moderate)] or sham surgery (Rosi et al 2012). After injury, the incision was closed with interrupted 6-0 silk sutures, anesthesia was terminated, and the animal was placed into a heated cage to maintain normal core temperature for 45-min post-injury.…”

Delayed Administration of Alpha-Difluoromethylornithine Prevents Hippocampus-Dependent Cognitive Impairment after Single and Combined Injury in Mice

“…All mice, regardless of injury type, were subjected to this surgical procedure. Mice that were randomly selected for the trauma only group (no irradiation) or the RCI treatment group were subjected to a controlled cortical impact (10, 11). The lesion was produced with a pneumatic impact device using a 3 mm diameter convex tip, mounted 20° from the vertical to account for the curvature of the mouse skull.…”

Dose- and ApoE Isoform-Dependent Cognitive Injury after Cranial56Fe Irradiation in Female Mice

“…The behaviorally-induced immediate early gene Arc was investigated by Rosi et al (2008Rosi et al ( , 2010 and Raber et al (2013) for its expression in the dentate gyrus of mice. Both messenger RNA and protein levels in neurons showed behaviorally-induced upregulation which was inhibited by exposure to X-rays and low doses of 56 Fe ions.…”