Neuroprotective effects of brilliant blue G on the brain following traumatic brain injury in rats.

Abstract

The P2X7 inhibitor, brilliant blue G (BBG), has been reported as a neuroprotective drug against a variety of disorders, including neuropathic pain and brain ischemia. Currently, no studies have examined the potential for BBG to provide neuroprotection in animal models of TBI. The aim of the present study was to investigate the neuroprotective effect of BBG on TBI and to determine the underlying mechanisms. The rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device, and then divided randomly into three groups: the sham-operated, BBG treatment and vehicle groups. In the BBG treatment group, 50 mg/kg brilliant blue G (BBG; 100% pure), a highly specific and clinically useful P2X7 antagonist, was administered via the tail vein 15 min prior to or up to 8 h following TBI. The co-localization of NeuN and protein kinase Cγ (PKCγ) was followed with immunofluorescent staining. The expression of P2X7, PKCγ and inflammatory cytokines was identified by western blot analysis. Wet-dry weight method was used to evaluate brain edema, and motor function outcome was examined using the neurological severity score. The present study demonstrated that the administration of BBG attenuated TBI-induced cerebral edema and the associated motor deficits. Following trauma, BBG treatment significantly reduced the levels of PKCγ and interleukin-1β in the cortex. The results provide in vivo evidence that BBG exerted neuroprotective effects by attenuating brain edema and improving neurological functions via reducing PKCγ and interleukin-1β levels following TBI.

• Authors: Yong-Chao Wang, Ying Cui, Jian-Zhong Cui, Li-Qian Sun, Chang-Meng Cui, Hong-Ao Zhang, Hui-Xing Zhu, Ran Li, Yan-Xia Tian, Jun-Ling Gao
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 2 Pg. 2149-54 (Aug 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25873133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Neuroprotective Agents
• Purinergic P2X Receptor Antagonists
• Receptors, Purinergic P2X7
• Rosaniline Dyes
• protein kinase C gamma
• Protein Kinase C
• coomassie Brilliant Blue

Topics

• Animals
• Brain (drug effects, pathology)
• Brain Edema (complications, drug therapy, pathology)
• Brain Injuries (complications, drug therapy, pathology)
• Interleukin-1beta (analysis)
• Neuroprotective Agents (therapeutic use)
• Protein Kinase C (analysis)
• Purinergic P2X Receptor Antagonists (therapeutic use)
• Rats, Sprague-Dawley
• Receptors, Purinergic P2X7 (analysis)
• Rosaniline Dyes (therapeutic use)