Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury.
OBJECTIVE
Traumatic brain injury (TBI) triggers a complex series of inflammatory responses that contribute to secondary tissue damage. The aim of this study was to investigate the effect of baicalein, a flavonoid possessing potent anti-inflammatory properties, on functional and histological outcomes and inflammatory cytokine expression, following TBI in rats.


METHODS
Rats subjected to controlled cortical impact injury were injected with baicalein (30 mg kg(-1)) or vehicle immediately after injury or daily for 4 days. Neurological status was evaluated using the rotarod, adhesive removal, modified neurological severity scores and beam walk tests. Contusion volume and neuronal degeneration were measured using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) mRNA and protein were assessed by real-time quantitative reverse transcriptase-PCR, enzyme-linked immunosorbent assay and immunohistochemistry.


RESULTS
Single-dose and multiple-dose treatment with baicalein significantly improved functional recovery and reduced contusion volumes up to day 28 post-injury, although multiple-dose baicalein was the more effective treatment. Single-dose baicalein also significantly reduced the number of degenerating neurons (31%) on post-injury day 1 as indicated by FJB staining. These changes were associated with significantly decreased levels, at the contusion site, of TNF-alpha, IL-1 beta and IL-6 mRNA at 6 h, and cytokine protein on day 1 post-injury.


CONCLUSIONS
Post-injury treatment with baicalein improved functional and histological outcomes and reduced induction of proinflammatory cytokines in rat TBI. The neuroprotective effect of baicalein may be related to a decreased inflammatory response following the injury.
Chen
S-F
SF
Department of Physical Medicine and Rehabilitation, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan, Republic of China.
Hsu
C-W
CW
Huang
W-H
WH
Wang
J-Y
JY
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D044950:Flavanones / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D044950:Flavanones; D018836:Inflammation Mediators; C006680:baicalein
Science. 1982 Aug 27;217(4562):855-7
7100929
J Neuroimmunol. 1990 Dec;30(2-3):213-7
2229409
Exp Neurol. 2007 May;205(1):270-8
17397834
J Neuroimmunol. 1999 Nov 15;101(2):211-21
10580806
J Pharmacol Exp Ther. 2003 May;305(2):638-45
12606597
Neurosci Lett. 1992 Dec 14;148(1-2):137-40
1300486
J Neurol Neurosurg Psychiatry. 1998 Nov;65(5):729-33
9810947
J Neural Transm (Vienna). 2005 Mar;112(3):331-47
15503194
J Cereb Blood Flow Metab. 1999 Oct;19(10):1118-25
10532636
Nat Rev Neurosci. 2001 Oct;2(10):734-44
11584311
Neuroreport. 1999 Feb 5;10(2):409-12
10203344
J Neurotrauma. 1998 Jun;15(6):399-409
9624625
Neuroscience. 2005;136(4):971-89
16242846
J Exp Med. 1996 Aug 1;184(2):717-24
8760825
J Neuroimmunol. 1999 Mar 1;95(1-2):115-25
10229121
Neuroscience. 2007 Dec 12;150(3):585-91
17942241
Stroke. 2006 Dec;37(12):3014-8
17053180
J Neurosurg. 1997 Mar;86(3):493-504
9046307
Chem Pharm Bull (Tokyo). 2003 Mar;51(3):339-40
12612426
Am J Chin Med. 1988;16(3-4):145-54
2854372
Pharmacol Res. 2001 Feb;43(2):173-8
11243719
Exp Neurol. 2003 Jul;182(1):87-102
12821379
Neurosurgery. 2004 Aug;55(2):416-24; discussion 424-5
15271250
Free Radic Biol Med. 2001 Feb 15;30(4):433-46
11182299
Eur J Pharmacol. 2003 Mar 28;465(1-2):171-81
12650847
Life Sci. 2007 Jul 4;81(4):288-98
17612572
Planta Med. 2001 Jun;67(4):331-4
11458449
Toxicology. 2006 Sep 21;226(2-3):238-45
16887252
Exp Neurol. 2005 May;193(1):125-30
15817271
J Neurotrauma. 2001 Nov;18(11):1207-16
11721739
J Neurotrauma. 2002 Sep;19(9):1039-50
12482117
J Neuroimmunol. 1997 Feb;72(2):169-77
9042110
J Neurosurg. 2000 Jan;92(1):108-20
10616089
J Neurotrauma. 2005 Aug;22(8):885-95
16083355
Trends Pharmacol Sci. 1998 Feb;19(2):59-66
9550943
J Pharmacol Sci. 2005 Jun;98(2):185-9
15942123
J Immunol. 1988 Oct 15;141(8):2629-34
3171180
Exp Eye Res. 2003 Aug;77(2):195-202
12873450
J Cereb Blood Flow Metab. 2004 Feb;24(2):133-50
14747740
Arch Biochem Biophys. 1993 Oct;306(1):261-6
8215413
Crit Rev Neurobiol. 2003;15(1):61-90
14513863
Stroke. 2001 Apr;32(4):1005-11
11283404
J Cereb Blood Flow Metab. 1999 Feb;19(2):184-94
10027774
Life Sci. 2002 Sep 20;71(18):2105-17
12204769
J Neuroimmunol. 1993 Feb;42(2):177-85
8429103
J Trauma. 2006 Jan;60(1):152-7
16456449
Am J Chin Med. 1998;26(3-4):311-23
9862019
Brain Res Mol Brain Res. 1996 Mar;36(2):287-91
8965649
J Cereb Blood Flow Metab. 1996 May;16(3):378-84
8621742
Toxicol Appl Pharmacol. 2006 Oct 15;216(2):263-73
16814338
J Cereb Blood Flow Metab. 1994 Jul;14(4):615-9
8014208
Dev Neurosci. 1994;16(3-4):172-9
7705222
Br J Pharmacol. 2002 Dec;137(8):1314-20
12466241
Neurol Res. 2001 Mar-Apr;23(2-3):175-82
11320596
J Neuroimmunol. 1999 Dec;100(1-2):203-15
10695731
Prog Neurobiol. 2002 Jun;67(2):161-72
12126659
Immunobiology. 2006;211(5):359-68
16716805
Brain Res. 2000 Aug 25;874(2):123-30
10960596
Biosci Biotechnol Biochem. 2006 Oct;70(10):2371-80
17031041
Curr Opin Crit Care. 2002 Apr;8(2):101-5
12386508
Brain Behav Immun. 1995 Dec;9(4):355-65
8903852
Planta Med. 2002 Mar;68(3):268-71
11914968
Shock. 2004 Aug;22(2):102-7
15257081
Neurosci Biobehav Rev. 2004 Jul;28(4):365-78
15341032