Abstract
A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls. The rats survived for either 48 h or 15 days post-injury. At 48 h, the animals were tested in the Morris water maze (MWM) for memory function and their brains analyzed for cerebral edema. Here, mFPI-induced brain edema compared to sham or naïve controls that was significantly reduced by AF-16 treatment (p < 0.05) although MWM performance was not altered. In the 15-day survival groups, the MWM learning and memory abilities as well as histological changes were analyzed. AF-16-treated brain-injured animals shortened both MWM latency and swim path in the learning trials (p < 0.05) and improved probe trial performance compared to brain-injured controls treated with the inactive reference peptide. A modest decrease by AF-16 on TBI-induced changes in hippocampal glial acidic fibrillary protein (GFAP) staining (p = 0.11) was observed. AF-16 treatment did not alter any other immunohistochemical analyses (degenerating neurons, beta-amyloid precursor protein (β-APP), and Olig2). In conclusion, intranasal AF-16-attenuated brain edema and enhanced visuospatial learning and memory following diffuse TBI in the rat. Intranasal administration early post-injury of a promising neuroprotective substance offers a novel treatment approach for TBI.
Highlights
Traumatic brain injury (TBI) is a global health problem caused by e.g. motor vehicle accidents, falls, assaults, as well as work and sports injuries [1,2,3,4]
These results suggest that antisecretory factor (AF)-16 is a promising neuroprotective treatment of TBI and that intranasal administration is an attractive alternative route for the delivery of potentially beneficial pharmacological compounds to the injured brain
The present study provides evidence that intranasal administration of the antisecretory peptide AF-16 attenuates the TBI-induced brain edema compared to an inactive reference scramble peptide in brain-injured rats at 48 h post-injury
Summary
Traumatic brain injury (TBI) is a global health problem caused by e.g. motor vehicle accidents, falls, assaults, as well as work and sports injuries [1,2,3,4]. The initial brain injury occurring at time of impact is markedly exacerbated over hours, days, and AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse TBI in Rats months by complex secondary cascades [5, 6]. In theory and as reported in many preclinical studies, these secondary injury factors should be amenable to pharmacological interventions resulting in improved clinical outcome. Despite extensive experimental research and many clinical trials, no pharmacological treatment has shown successful results in TBI patients [7]. The mechanisms behind the development of post-traumatic brain edema are complex, and both cytotoxic and vasogenic components contribute to the increase in brain water content (BWC) [7]
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