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Updated: Jul 4, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Traumatic brain injury-induced disruption of the circadian clock
Lu-Ting Kuo1,2, Hsueh-Yi Lu3, Yi-Hsing Chen4
1Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chun-Shan South Road, Taipei, 100, Taiwan. kuoluting@gmail.com.
Insights
Traumatic brain injury (TBI) disrupts circadian rhythms. This study found that acute subdural hematoma in rats altered the rhythmic expression of key circadian genes (Per2, Cry1, Bmal1) in blood cells and disrupted body temperature regulation.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Circadian rhythm disturbances are common after traumatic brain injury (TBI).
- The expression of circadian genes in peripheral blood leukocytes (PBL) following TBI remains uninvestigated.
- Acute subdural hematoma (ASDH) is a severe form of TBI.
Purpose of the Study:
- To investigate the mRNA expression of circadian genes in PBLs of rats with ASDH.
- To assess the impact of ASDH on the rhythmic expression of specific circadian genes (Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock).
- To evaluate changes in body temperature rhythm following ASDH.
Main Methods:
- Quantification of circadian gene mRNA expression in PBLs from sham-operated and ASDH rats over 48 hours.
- Measurement of rectal temperature every 4 hours over 2 days in both groups.
- Cosinor analysis to estimate mesor, rhythm, amplitude, and acrophase of gene expression and body temperature.
Main Results:
- Rhythmic expression of Per2, Cry1, and Bmal1 mRNAs was observed in sham-operated rats' PBLs.
- ASDH rats exhibited disrupted rhythmicity in Per2, Cry1, and Bmal1 mRNA expression.
- ASDH rats showed a disrupted rectal temperature rhythm, with diminished amplitude and acrophase shift compared to sham-operated rats.
Conclusions:
- ASDH in rats leads to dysregulated expression of specific circadian genes in PBLs.
- TBI with ASDH significantly alters body temperature rhythmicity.
- Further research is needed to elucidate the pathophysiology of disrupted circadian networks post-TBI.
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.
