Abstract
Purpose: To investigate the effect of bisleuconothine A (BA), alone and in combination with hyperbaric oxygen (HO), on traumatic brain injury (TBI) in rats.
 Methods: Traumatic brain injury (TBI) was induced by dropping a 200-g weight of steel on the left anterior frontal areas of Sprague-Dawley rats. The synergistic effect of BA and HO was determined by assessing neurological score, as well as parameters of oxidative stress and inflammation, expressions of P2X4 protein and other proteins, and levels of reactive oxygen species (ROS) in the brain tissues of TBI rats.
 Results: Neurological function score, levels of inflammatory mediators and oxidative stress parameters were significantly reduced in rats treated with BA alone, and in those treated with a combination of BA and HO, when compared with untreated TBI rats (p < 0.01). Moreover, treatment with BA alone, and BA-HO combination attenuated the altered protein expressions of P2X4, Akt, PI3K and TLR-4 in the TBI rats, and also upregulated the mRNA expression of P2X4 in the brain tissue, when compared with untreated TBI rats (p < 0.01).
 Conclusion: These results suggest that BA, when used alone or in combination with HO, reduces neuronal injury through upregulation of the protein expression of P2X4 in rats with traumatic brain injury. Thus, BA may be used clinically with HO therapy for the management of traumatic injury.
 Keywords: Bisleuconothine A, Hyperbaric oxygen, Neuronal injury, Oxidative stress, Inflammatory mediators
Highlights
Traumatic brain injury (TBI) is one of the major causes of death worldwide
Rats in bisleuconothine A (BA)+hyperbaric oxygen (HO) group showed higher reduction in modified neurological severity score (mNSS) than those in TBI and HO groups. These results suggest that the treatment with combination of BA and HO produced synergistic effect on mNSS in TBI rats
The present study determined the protective effect of bisleuconothine A (BA) alone, and in combination with hyperbaric oxygen (HO), on secondary injury in TBI rats
Summary
Traumatic brain injury (TBI) is one of the major causes of death worldwide. It is well documented that hyperbaric oxygen ameliorates neuronal damage, it has many limitations. The present investigation was carried out to study the effects of bisleuconothine A and hyperbaric oxygen on traumatic neuronal injury in rats. Traumatic brain injury was induced in the rats after removing their fur. Hyperbaric oxygen (HO) was administered as per previously published reports [10]. The rats were treated with pure oxygen for 10 min by placing them in a chamber containing 95% oxygen. The mNSS was calculated on a 0–18 scale, where 0 indicated normal brain function, and 18 indicated a severe deficit
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