Adenosine, lidocaine, and Mg2+ (ALM) resuscitation fluid protects against experimental traumatic brain injury

Abstract

Background: Currently, no drug therapy prevents secondary injury progression after traumatic brain injury (TBI). Our aim was to investigate the effects of small-volume intravenous adenosine, lidocaine, and Mg (ALM) resuscitation fluid after moderate TBI in a rat fluid-percussion injury model.

Methods: Anesthetized, mechanically ventilated male Sprague-Dawley rats (449 ± 5 g) were randomly assigned to one of four groups: (1) sham (craniotomy without TBI), (2) no-treatment, (3) saline-control, or (4) ALM therapy groups (all n = 16). A subdural probe was implanted in eight animals per group to measure cerebral blood flow. Fifteen minutes after moderate TBI was induced with lateral fluid percussion injury (2.57 atm), a single 3% NaCl ± ALM bolus (0.7 mL/kg) was injected intravenously, and after 60 minutes (Phase 1), 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was administered for 3 hours (Phase 2).

Results: Mortality (without subdural brain probe) was 25% (saline controls) and 0% (ALM). Sixty minutes after bolus, ALM significantly increased cardiac function, cortical blood flow (CBF; approximately threefold) and blunted systemic inflammation compared to saline controls. Three hours after infusion drip, ALM improved left ventricular function, supported higher CBF, decreased proinflammatory cytokines systemically (IL-1β, tumor necrosis factor α, and regulated on activation, normal T cell expressed and secreted [RANTES]), increased anti-inflammatory cytokines in brain tissue (IL-10, IL-4), lowered brain injury markers (neuron-specific enolase, Syndecan-1, HMGB-1), reduced coagulopathy, increased platelet aggregation, and maintained baseline fibrinogen levels. Saline-controls were proinflammatory (brain, heart, lung, and blood) and hypocoagulable with neurogenic enlargement of the right side of the heart. Survival time significantly correlated with plasma neuron-specific enolase (p = 0.001) and CBF at 180 minutes (p = 0.009), and CBF correlated with brain anti-inflammatory cytokines (p = 0.001-0.034).

Conclusion: After moderate TBI, ALM resuscitation fluid increased survival and protected against early secondary injury by reducing coagulopathy, inflammation, and platelet dysfunction.