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

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.

BAY61‑3606 attenuates neuroinflammation and neurofunctional damage by inhibiting microglial Mincle/Syk signaling response after traumatic brain injury

“…This system is widely used to assess the degree of nerve injury in central nerve system disease. The test was operated on days 1, 3, 7, 14 and 28 by three individuals through a triple-blind manner, and the scores were averaged ( 38 , 39 ).…”

Characterising severe traumatic brain injury from fresh cerebral biopsy in living patients

“…Neurones from non-injured brain immunostained with NeuN exhibited a large round or polygonal cell body with staining in both the nuclei and cytoplasm, and some proximal processes 9,25,26 . However, neuronal atrophy, vacuoles in the cytoplasm, and neuronal cell loss were observed after injury 27 .…”

“…The stained brain sections were evaluated blind to the patient's early clinical condition by PKY who has more than twenty years of histological experience with immunohistochemistry in traumatic CNS injuries, involving neuronal injury 14,20 , dendritic injury 21 , neurovascular injury 9 , and neuroinflammation 10,14 . The Glasgow Outcome Scale-Extended (GOS-E) at 3 months post injury was used to define the outcome of the patients as it is validated as a good indicator of severity, disability, cognitive dysfunction, and health in TBI patients [22][23][24] .…”

“…Medical imaging, while currently the cornerstone of TBI diagnosis, is as yet unable to detect important microscopic cellular changes due to a lack of spatial resolution. TBI can lead to various types of pathophysiological events such as neuronal injury, dendritic injury, neurovascular disruption, and neuroinflammation, [8][9][10] . These cellular and molecular changes occur at microscopic levels and by the time clinical deterioration such as raised ICP, pupillary abnormalities or neuroimaging changes occur, it is often too late for effective treatment.…”

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

“…Experimental studies have also presented a better brain delivery of other drugs, such as antiepileptic drugs or docosahexaenoic acid (DHA), in hypertonicity-related hyperpermeability of the BBB [93,94]. Interestingly, an increase of DHA attenuates BBB disruption, and reduces cerebral edema and TBI-induced neuroinflammation [94,95]. It is difficult to show a destructive effect of plasma hyperosmolality on the BBB in patients treated for TBI.…”