Long-term cognitive impairment without diffuse axonal injury following repetitive mild traumatic brain injury in rats

Sai Ambika Tadepalli, Zsolt Kristóf Bali, Nóra Bruszt, Lili Veronika Nagy, Krisztina Amrein, Bálint Fazekas, A. Büki, Endre Czeiter, I. Hernádi

Research output: Article

Abstract

Repetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI – 5 hits, 24 h apart), rapid repetitive mild (rapTBI – 5 hits, 5 min apart) or a single severe (sTBI) TBI. Cognitive performance was assessed 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6–7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were evaluated 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than the Sham and mTBI groups. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β. Results suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries and that the prolonged cognitive impairment after repetitive mild TBI originates from different structural and molecular mechanisms compared to similar impairments after single sTBI.

Original languageEnglish
Article number112268
JournalBehavioural Brain Research
Volume378
DOIs
Publication statusPublished - jan. 27 2020

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Diffuse Axonal Injury
Brain Concussion
Wounds and Injuries
Enzyme-Linked Immunosorbent Assay
Aptitude
Craniocerebral Trauma
Neurodegenerative Diseases
Cognitive Dysfunction
Biomarkers
Immunohistochemistry
Traumatic Brain Injury
Weights and Measures
Water
Serum

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Long-term cognitive impairment without diffuse axonal injury following repetitive mild traumatic brain injury in rats. / Tadepalli, Sai Ambika; Bali, Zsolt Kristóf; Bruszt, Nóra; Nagy, Lili Veronika; Amrein, Krisztina; Fazekas, Bálint; Büki, A.; Czeiter, Endre; Hernádi, I.

In: Behavioural Brain Research, Vol. 378, 112268, 27.01.2020.

Research output: Article

Tadepalli, Sai Ambika ; Bali, Zsolt Kristóf ; Bruszt, Nóra ; Nagy, Lili Veronika ; Amrein, Krisztina ; Fazekas, Bálint ; Büki, A. ; Czeiter, Endre ; Hernádi, I. / Long-term cognitive impairment without diffuse axonal injury following repetitive mild traumatic brain injury in rats. In: Behavioural Brain Research. 2020 ; Vol. 378.
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abstract = "Repetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI – 5 hits, 24 h apart), rapid repetitive mild (rapTBI – 5 hits, 5 min apart) or a single severe (sTBI) TBI. Cognitive performance was assessed 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6–7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were evaluated 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than the Sham and mTBI groups. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β. Results suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries and that the prolonged cognitive impairment after repetitive mild TBI originates from different structural and molecular mechanisms compared to similar impairments after single sTBI.",
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AU - Tadepalli, Sai Ambika

AU - Bali, Zsolt Kristóf

AU - Bruszt, Nóra

AU - Nagy, Lili Veronika

AU - Amrein, Krisztina

AU - Fazekas, Bálint

AU - Büki, A.

AU - Czeiter, Endre

AU - Hernádi, I.

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AB - Repetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI – 5 hits, 24 h apart), rapid repetitive mild (rapTBI – 5 hits, 5 min apart) or a single severe (sTBI) TBI. Cognitive performance was assessed 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6–7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were evaluated 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than the Sham and mTBI groups. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β. Results suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries and that the prolonged cognitive impairment after repetitive mild TBI originates from different structural and molecular mechanisms compared to similar impairments after single sTBI.

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KW - Chronic traumatic encephalopathy

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KW - Memory

KW - Novel object recognition

KW - Water maze

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