DHA Attenuates Cerebral Edema Following Traumatic Brain Injury via the Reduction in Blood-Brain Barrier Permeability.

Zhuo-Hao Liu,Shao-Chieh Chiu,Siew-Na Lim,Ping K Yip,Ying-Cheng Huang,Nan-Yu Chen,Chen-Te Wu,Po-Hsun Tu

doi:10.3390/ijms21176291

Abstract

Traumatic brain injury (TBI) could result in edema and cause an increase in intracranial pressure of the brain resulting in mortality and morbidity. Although there is hyperosmolarity therapy available for this pathophysiological event, it remains controversial. Recently, several groups have shown docosahexaenoic acid (DHA) to improve functional and histological outcomes following brain injury based on reduction of neuroinflammation and apoptosis. However, the effect of DHA on blood–brain barrier (BBB) dysfunction after brain injury has not been fully studied. Here, a controlled cortical impact rat model was used to test the effect of a single dose of DHA administered 30 min post injury. Modified neurological severity score (mNSS) and forelimb asymmetry were used to determine the functional outcomes. Neuroimaging and histology were used to characterize the edema and BBB dysfunction. The study showed that DHA-treated TBI rats had better mNSS and forelimb asymmetry score than vehicle-treated TBI rats. Temporal analysis of edema using MRI revealed a significant reduction in edema level with DHA treatment compared to vehicle in TBI rats. Histological analysis using immunoglobulin G (IgG) extravasation showed that there was less extravasation, which corresponded with a reduction in aquaporin 4 and astrocytic metalloprotease 9 expression, and greater endothelial occludin expression in the peri-contusional site of the TBI rat brain treated with DHA in comparison to vehicle treatment. In conclusion, the study shows that DHA can exert its functional improvement by prevention of the edema formation via prevention of BBB dysfunction after TBI.

Highlights

Traumatic brain injury (TBI) can affect people of all ages and is a major cause of death and disability, with an incidence of approximately 10 million people worldwide [1]
There was a significant difference in the Modified neurological severity score (mNSS) score between the docosahexaenoic acid (DHA)-treated (7.9 ± 0.3) and vehicle-treated TBI rats (7.9 ± 0.1) in comparison to the sham-operated rats (0.7 ± 0.7) at 1 day post injury (Figure 1A)
The significant difference between DHA-treated and vehicle-treated TBI rats remained significantly different at day 3 and 4 post injury (Figure 1B)

Summary

Introduction

Traumatic brain injury (TBI) can affect people of all ages and is a major cause of death and disability, with an incidence of approximately 10 million people worldwide [1]. One example is the use of omega-3 polyunsaturated fatty acid that is essential in normal brain development involved in cognition and other brain functions [4]. Recent studies have demonstrated that dietary depletion of omega-3 fatty acid during gestation and postnatal development can induce cognitive deficits and exacerbated neuronal death after TBI [5]. In a more therapeutically applicable scenario, a study that had provided TBI rats with dietary supplementation for 1 month after injury showed decreased TBI-induced axonal damage and apoptosis [6]. Another study that injected omega-3 fatty acid intraperitoneally 30 min post injury and daily for 1 week demonstrated an attenuation of TBI-induced neuronal apoptosis [7]. A spinal cord injury study in rodents showed that DHA but not EPA can reduce early inflammatory response [8]. EPA has shown to accelerate the disease progression of amyotrophic lateral sclerosis in a rodent model [9]

Methods

Results

Conclusion