Traumatic brain injury-induced disruption of the circadian clock

Abstract Disturbances in the circadian rhythm have been reported in patients following traumatic brain injury (TBI). However, the rhythmic expression of circadian genes in peripheral blood leukocytes (PBL) following TBI has not yet been studied. The messenger ribonucleic acid (mRNA) expression of period 1 ( Per1 ), Per2 , Per3 , cryptochrome 1 ( Cry1 ), Cry2 , brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 ( Bmal1 ), and circadian locomotor output cycles kaput ( Clock ) was quantified in PBLs from sham-operated rats and rats with acute subdural hematoma (ASDH) over a 48-h period. The rectal temperature of the animals was measured every 4 h over 2 days. The mesor, rhythm, amplitude, and acrophase were estimated using cosinor analysis. Cosinor analysis revealed that Per2 , Cry1 , and Bmal1 mRNAs were rhythmically expressed in the PBLs of sham-operated rats. In contrast, fluctuations in rhythmic expression were not observed following ASDH. The rectal temperature of sham-operated rats also exhibited rhythmicity. ASDH rats had a disrupted rectal temperature rhythm, a diminished amplitude, and an acrophase shift. TBI with ASDH results in dysregulated expression of some circadian genes and changes in body temperature rhythm. Further research is required to understand the pathophysiology of altered circadian networks following TBI. Key messages First to investigate the mRNA expression of circadian genes in PBLs of ASDH rats. ASDH rats had disrupted rhythmicity of Per2, Cry1, and Bmal1 mRNA expression. Cosinor analysis showed that ASDH rats had a disrupted rectal temperature rhythm.