AA-861 appears to suppress leukocyte infiltration induced by traumatic brain injury in rats.
OBJECTIVE
To study the effect of 2,3,5-Trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861) on intercellular adhesion molecule 1 (ICAM-1) and P-selectin expression, leukotriene B4 (LTB4) level, and myeloperoxidase (MPO) activity 24 hours after traumatic brain injury (TBI).


METHODS
This study was carried out in the laboratory of the Department of Clinical Pharmacology, Osmangazi University, Eskisehir, Turkey in 2006. Traumatic brain injury was induced in 2 sets of animals using Feeney`s weight-drop method. The first set was used to study the expression of ICAM-1, P-selectin, CD11a, and mouse anti-rat granulocyte monoclonal antibody (HIS48). The second was used to study tissue changes in LTB4 level, and MPO activity. The rats were sacrificed at 0.5, 4, 24, 48, and 72 hours post-injury.


RESULTS
Intercellular adhesion molecule (p=0.000001) and P-selectin expression (p=0.00002) peaked at 24 hours, remained high at 48 hours (p=0.00012 for ICAM-1, and p=0.00002 for P-selectin), and 72 hours (p=0.000008 for ICAM-1, p=0.0011 for P-selectin). The HIS48 intensity was significantly increased at 24-72 hours (p=0.022), while the intensity of CD11a became significant only at 72 hours (p=0.040). Myeloperoxidase activity increased notably at 24 hours (p=0.00077), and peaked at 48 hours (p=0.00001). The LTB4 increased markedly at 4 hours (p=0.000004), and peaked at 24 hours (p=0.000001). Pretreatment with AA-861 considerably suppressed the expression of ICAM-1 (p=0.0053), and P-selectin (p=0.0018) on microvascular endothelium, and lowered MPO activity (p=0.0007), and LTB4 level (p=0.008) at 24 hours.


CONCLUSIONS
The present results suggest that AA-861 might be a potential mediator in the treatment of brain inflammation in TBI.
Department of Neurosurgery, Medical School of Eskisehir Osmangazi University, Eskisehir, Turkey. rdurmaz@ogu.edu.tr.
Ramazan
R
Durmaz
Emine
E
Kasapoglu
Murat
M
Vural
Ömer
Ö
Çolak
Yüksel
Y
Aydar
Cengiz
C
Bal
Metin A
MA
Atasoy