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

Abstract

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. 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. 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. 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.