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

摘要

BACKGROUND beta-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of beta-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 beta-blocker group (n = 10) or the placebo group (n = 10). Mice in the beta-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 beta-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. beta-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The beta-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-1 beta, IL-6, and TNF-alpha. The beta-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 beta-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.