Daily quetiapine after severe TBI improves learning and memory.

Abstract

Background: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI.

Methods: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on Day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction ( p < 0.05).

Results: On Day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 ( p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 ( p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones ( p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones ( p < 0.05).

Conclusion: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.