Neuroprotective effects of dexmedetomidine combined with targeted temperature management on brain edema in traumatic brain injury

Abstract

Objective To explore the neuroprotective effects of dexmedetomidine (Dex) combined with targeted temperature management (TTM) on brain edema in traumatic brain injury (TBI) mice. Methods A total of 132 male C57BL/6 mice were randomly divided into normal group, sham-operation (Sham) group, traumatic brain injury (TBI) group, targeted temperature management (TTM) group, dexmedetomidine (Dex) group, and combination with TTM and Dex (DT) group, respectively (n=22 per group). The TBI animal model was established by electric controlled cortical impactor (eCCI), and then settled promptly on a mild hypothermic blanket (targeted temperature of (32±1)℃) for 6 h, or intraperitoneal injection of Dex (20 μl/kg) at 0, 2 and 4 h after TBI. Neurological function and spatial learning and memory ability were evaluated by modified neurological severity scores (mNSS) and Morris water maze (MWM), respectively. Then, mice were sacrificed at 24 h after TBI and stained using hematoxylin and eosin (H & E). Additionally, the cerebral edema was evaluated from the water content of the brain tissue using the wet-to-dry weight ratio, and the expression of aquaporin 4 (AQP4) was measured by Western blot assay. Results Compared with the Sham group, TBI mice showed neurologic deficits ((13.2±3.0) vs (0.5±0.7))(P<0.01), spatial learning and memory capacity decline((2.9±1.0) vs (7.4±1.3))( P<0.05), and the brain water content and the expression of AQP4 were increased ((79.81±0.80)% vs (75.98±0.62)%): ((1.60±0.07) vs (0.73±0.03))(all P<0.01). However, Dex or TTM could improve the neurological function(Dex: (10.3±2.8), TTM: (10.0±2.9)), reduce the brain water content(Dex: (78.50±0.40)%, TTM: (78.10±0.45)%), and significantly decrease the expression of AQP4 compared with the TBI group(Dex: (1.40±0.04), TTM: (1.15±0.12)) (all P<0.05), especially that of DT group ((9.2±2.5) , (5.4±1.8) , (77.67±0.30)%, (0.93±0.09)) (all P<0.01). Conclusion These finding suggests that Dex combined with targeted temperature management can reduce cerebral edema and improve neurological outcome in mice after TBI to exert neuroprotection effect, which may be related with the down-regulation of AQP4 protein. Key words: Traumatic brain injury; Dexmedetomidine; Targeted temperature management; Brain edema