Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury

Muhammad Zeeshan, Mohammad Hamidi, Terence O'Keeffe, Esther H. Bae, Kamil Hanna, Randall S. Friese, Narong Kulvatunyou, El Rasheid Zakaria, Lynn Gries, Andrew Tang, Bellal Joseph

Research output: Contribution to journalArticle

Abstract

BACKGROUND: β-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI. STUDY DESIGN: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the β-blocker group (n = 10) or the placebo group (n = 10). Mice in the β-blocker group received intraperitoneal 4 mg/kg propranolol every 24 hours for 7 days while the placebo group received 4 mg/kg normal saline. Baseline novel object recognition and classic maze tests were done prior to TBI and then daily from Day 1 through 7 after TBI. Animals were sacrificed on Day 7. Serum biomarkers were measured using ELISA and brain sections were analyzed using western blot and hematoxylin and eosin staining. RESULTS: Both the β-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. β-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The β-blocker group required less time to complete the maze-test compared to placebo group after Day 4. There was no difference regarding the serum levels of IL-1β, IL-6, and TNF-α. The β-blocker group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain lysate. Hematoxylin and eosin staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo group compared with the β-blocker group. CONCLUSION: Postinjury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of antiapoptotic protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared with the placebo.

Original languageEnglish (US)
Pages (from-to)1140-1147
Number of pages8
JournalJournal of Trauma and Acute Care Surgery
Volume87
Issue number5
DOIs
StatePublished - Nov 1 2019

Fingerprint

Memory Disorders
Propranolol
Learning
Placebos
Cognition
Hematoxylin
Eosine Yellowish-(YS)
Staining and Labeling
Traumatic Brain Injury
Brain
Serum
Interleukin-1
Inbred C57BL Mouse
Interleukin-6
Cell Death
Biomarkers
Western Blotting
Enzyme-Linked Immunosorbent Assay
Apoptosis
Neurons

Keywords

  • Beta blockers
  • Propranolol
  • Traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury. / Zeeshan, Muhammad; Hamidi, Mohammad; O'Keeffe, Terence; Bae, Esther H.; Hanna, Kamil; Friese, Randall S.; Kulvatunyou, Narong; Zakaria, El Rasheid; Gries, Lynn; Tang, Andrew; Joseph, Bellal.

In: Journal of Trauma and Acute Care Surgery, Vol. 87, No. 5, 01.11.2019, p. 1140-1147.

Research output: Contribution to journalArticle

Zeeshan, M, Hamidi, M, O'Keeffe, T, Bae, EH, Hanna, K, Friese, RS, Kulvatunyou, N, Zakaria, ER, Gries, L, Tang, A & Joseph, B 2019, 'Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury', Journal of Trauma and Acute Care Surgery, vol. 87, no. 5, pp. 1140-1147. https://doi.org/10.1097/TA.0000000000002484
Zeeshan, Muhammad ; Hamidi, Mohammad ; O'Keeffe, Terence ; Bae, Esther H. ; Hanna, Kamil ; Friese, Randall S. ; Kulvatunyou, Narong ; Zakaria, El Rasheid ; Gries, Lynn ; Tang, Andrew ; Joseph, Bellal. / Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury. In: Journal of Trauma and Acute Care Surgery. 2019 ; Vol. 87, No. 5. pp. 1140-1147.
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abstract = "BACKGROUND: β-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI. STUDY DESIGN: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the β-blocker group (n = 10) or the placebo group (n = 10). Mice in the β-blocker group received intraperitoneal 4 mg/kg propranolol every 24 hours for 7 days while the placebo group received 4 mg/kg normal saline. Baseline novel object recognition and classic maze tests were done prior to TBI and then daily from Day 1 through 7 after TBI. Animals were sacrificed on Day 7. Serum biomarkers were measured using ELISA and brain sections were analyzed using western blot and hematoxylin and eosin staining. RESULTS: Both the β-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. β-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The β-blocker group required less time to complete the maze-test compared to placebo group after Day 4. There was no difference regarding the serum levels of IL-1β, IL-6, and TNF-α. The β-blocker group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain lysate. Hematoxylin and eosin staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo group compared with the β-blocker group. CONCLUSION: Postinjury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of antiapoptotic protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared with the placebo.",
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AU - Zeeshan, Muhammad

AU - Hamidi, Mohammad

AU - O'Keeffe, Terence

AU - Bae, Esther H.

AU - Hanna, Kamil

AU - Friese, Randall S.

AU - Kulvatunyou, Narong

AU - Zakaria, El Rasheid

AU - Gries, Lynn

AU - Tang, Andrew

AU - Joseph, Bellal

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N2 - BACKGROUND: β-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI. STUDY DESIGN: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the β-blocker group (n = 10) or the placebo group (n = 10). Mice in the β-blocker group received intraperitoneal 4 mg/kg propranolol every 24 hours for 7 days while the placebo group received 4 mg/kg normal saline. Baseline novel object recognition and classic maze tests were done prior to TBI and then daily from Day 1 through 7 after TBI. Animals were sacrificed on Day 7. Serum biomarkers were measured using ELISA and brain sections were analyzed using western blot and hematoxylin and eosin staining. RESULTS: Both the β-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. β-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The β-blocker group required less time to complete the maze-test compared to placebo group after Day 4. There was no difference regarding the serum levels of IL-1β, IL-6, and TNF-α. The β-blocker group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain lysate. Hematoxylin and eosin staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo group compared with the β-blocker group. CONCLUSION: Postinjury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of antiapoptotic protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared with the placebo.

AB - BACKGROUND: β-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI. STUDY DESIGN: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the β-blocker group (n = 10) or the placebo group (n = 10). Mice in the β-blocker group received intraperitoneal 4 mg/kg propranolol every 24 hours for 7 days while the placebo group received 4 mg/kg normal saline. Baseline novel object recognition and classic maze tests were done prior to TBI and then daily from Day 1 through 7 after TBI. Animals were sacrificed on Day 7. Serum biomarkers were measured using ELISA and brain sections were analyzed using western blot and hematoxylin and eosin staining. RESULTS: Both the β-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. β-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The β-blocker group required less time to complete the maze-test compared to placebo group after Day 4. There was no difference regarding the serum levels of IL-1β, IL-6, and TNF-α. The β-blocker group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain lysate. Hematoxylin and eosin staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo group compared with the β-blocker group. CONCLUSION: Postinjury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of antiapoptotic protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared with the placebo.

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