The interaction of the circadian and immune system: Desynchrony as a pathological outcome to traumatic brain injury.

Traumatic brain injury (TBI) is a complex and costly worldwide phenomenon that can lead to many negative health outcomes including disrupted circadian function. There is a bidirectional relationship between the immune system and the circadian system, with mammalian coordination of physiological activities being controlled by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN receives light information from the external environment and in turn synchronizes rhythms throughout the brain and body. The SCN is capable of endogenous self-sustained oscillatory activity through an intricate clock gene negative feedback loop. Following TBI, the response of the immune system can become prolonged and pathophysiological. This detrimental response not only occurs in the brain, but also within the periphery, where a leaky blood brain barrier can permit further infiltration of immune and inflammatory factors. The prolonged and pathological immune response that follows TBI can have deleterious effects on clock gene cycling and circadian function not only in the SCN, but also in other rhythmic areas throughout the body. This could bring about a state of circadian desynchrony where different rhythmic structures are no longer working together to promote optimal physiological function. There are many parallels between the negative symptomology associated with circadian desynchrony and TBI. This review discusses the significant contributions of an immune-disrupted circadian system on the negative symptomology following TBI. The implications of TBI symptomology as a disorder of circadian desynchrony are discussed.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

OBJECTIVES: Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. METHODS: Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. RESULTS: Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. CONCLUSION: These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Sex differences in object location memory and spatial navigation in Long-Evans rats.

In both humans and rodents, males typically excel on a number of tasks requiring spatial ability. However, human females exhibit advantages in memory for the spatial location of objects. This study investigated whether rats would exhibit similar sex differences on a task of object location memory (OLM) and on the watermaze (WM). We predicted that females should outperform males on the OLM task and that males should outperform females on the WM. To control for possible effects of housing environment, rats were housed in either complex environments or in standard shoebox housing. Eighty Long-Evans rats (40 males and 40 females) were housed in either complex (Complex rats) or standard shoebox housing (Control rats). Results indicated that males had superior performance on the WM, whereas females outperformed males on the OLM task, regardless of housing environment. As these sex differences cannot be easily attributed to differences in cognitive style related to linguistic processing of environmental features or to selection pressures related to the hunting gathering evolutionary prehistory of humans, these data suggest that sex differences in spatial ability may be related to traits selected for by polygynous mating strategies.