Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury.
J Trauma Acute Care Surg
; 87(5): 1140-1147, 2019 11.
Article
in En
| MEDLINE
| ID: mdl-31425494
ABSTRACT
BACKGROUND:
ß-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of ß-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. STUDYDESIGN:
Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the ß-blocker group (n = 10) or the placebo group (n = 10). Mice in the ß-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 ß-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. ß-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The ß-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-1ß, IL-6, and TNF-α. The ß-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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Propranolol
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Adrenergic beta-Antagonists
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CA1 Region, Hippocampal
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Brain Injuries, Traumatic
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Memory Disorders
Type of study:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
/
Prognostic_studies
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
J Trauma Acute Care Surg
Year:
2019
Document type:
Article