Restorative Neurology and Neuroscience - Volume 32, issue 5

Authors: Moritz, Kasey E. | Geeck, Katalin | Underly, Robert G. | Searles, Madeleine | Smith, Jeffrey S.

Article Type: Research Article

Abstract: Purpose: Anxiety-like (ANX) and depression-like (DEP) symptoms are common consequences of traumatic brain injury (TBI). Environmental enrichment (EE) attenuates many deficits, though its impact on ANX and DEP symptoms has yet to be described. Methods: Adult male Long-Evans rats were subject to a medial frontal cortex (mFC) cortical impact injury or sham preparation, then placed into EE or standard housing (SE). ANX symptoms were analyzed using the open field test (OFT) and elevated plus maze (EPM). The forced swim task (FST) and sucrose consumption task (SCT) were used to quantify DEP symptoms. In order to measure changes in spatial learning …and motor performance, the Barnes maze (BM) and rotor rod (RR) were utilized. Results: Damage to the mFC resulted in functional losses in motor and cognitive behavior and an increase in ANX and DEP symptoms. Placement of injured rats into the EE improves motor functioning after TBI and resulted in an decreased latency to locate the escape box in the BM. Though the application of an EE attenuated deficits in BM and RR performance, the ANX and DEP behavioral symptoms persisted. Conclusions: Additional therapeutic approaches paired with EE may be necessary to address all functional changes post-TBI. Additionally, no single behavioral assessment appears to clearly identify symptoms of ANX or DEP in rats following TBI, however utilizing multiple tests can be potentially confounding. Show more

Keywords: Traumatic brain injury, anxiety, depression, enriched environment, stereology

DOI: 10.3233/RNN-140414

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 5, pp. 701-716, 2014

Authors: Israelsson, Charlotte | Flygt, Johanna | Åstrand, Elaine | Kiwanuka, Olivia | Bengtsson, Henrik | Marklund, Niklas

Article Type: Research Article

Abstract: Purpose: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from …brains of young adult male C57BL/6 mice at one, three or seven days following controlled cortical impact TBI or sham injury. Hippocampal and neocortical tissue ipsi- and contralateral to the injury was analyzed for Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), MAG, and the MAI receptors PirB and NgR1, including its co-receptor Lingo1. Results: Compared to sham-injured controls, PirB neocortical expression was significantly upregulated at one day and NgR1 expression downregulated at seven days post-TBI. In the hippocampus, transcriptional upregulation was observed in Nogo-A (one day post-injury), MAG and PirB at seven days post-injury. In contrast, the hippocampal transcripts of NgR1 and Lingo1 were decreased at seven days post-injury. The expression of OMgp was unaltered at all time points post-injury. Conclusion: These results suggest that early dynamic changes in MAI gene expression occur following TBI in the mouse, particularly in the hippocampus, which may play an inhibitory role for post-injury regeneration and plasticity. Show more

Keywords: TBI, mice, Nogo-A, Lingo1, Nogo-66 receptor 1, oligodendrocyte-myelin glycoprotein, myelin-associated glycoprotein

DOI: 10.3233/RNN-140419

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 5, pp. 717-731, 2014