Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate.
Traumatic brain injury causes development of posttraumatic epilepsy. Bleeding within neuropil is followed by hemolysis and deposition of hemoglobin in neocortex. Iron from hemoglobin and transferring is deposited in brains of patients with posttraumatic epilepsy. Iron compounds form reactive free radical oxidants. Microinjection of ferric ions into rodent brain results in chronic recurrent seizures and liberation of glutamate into the neuropil, as is observed in humans with epilepsy. Termination of synaptic effects of glutamate is by removal via transporter proteins. EAAC-1 is within neurons while GLT-1 and GLAST are confined to glia. Persistent down regulation of GLAST production is present in hippocampal regions in chronic seizure models. Down regulation of GLAST may be fundamental to a sequence of free radical reactions initiated by brain injury with hemorrhage. Administration of antioxidants to animals causes interruption of the sequence of brain injury responses induced by hemorrhage, suggesting that such a strategy needs to be evaluated in patients with traumatic brain injury.
Willmore
L J
LJ
Department of Neurology & Psychiatry, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MI 63104, USA. willmore@slu.edu
Ueda
Yuto
Y
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction
D000975:Antioxidants; D005609:Free Radicals; D050491:Glutamate Plasma Membrane Transport Proteins; D009569:Nitric Oxide; D018698:Glutamic Acid
N Engl J Med. 1998 Jan 1;338(1):20-4
9414327
Brain Res. 1983 Oct 31;277(2):393-6
6315151
Arch Neurol. 1979 Jan;36(1):8-12
105690
Exp Brain Res. 2002 Nov;147(2):219-26
12410337
J Neurochem. 1980 Jun;34(6):1630-8
7381489
Ann Neurol. 1989 Sep;26(3):321-30
2508534
Neurology. 1981 Jan;31(1):63-9
7192826
Nature. 1993 Aug 5;364(6437):535-7
7687749
Epilepsia. 1976 Jun;17(2):207-15
820549
J Neurosurg. 1999 Oct;91(4):593-600
10507380
Pathophysiology. 2002 Jun;8(3):205-214
12039653
Science. 1978 Jun 30;200(4349):1501-3
96527
Trends Pharmacol Sci. 1990 Nov;11(11):462-8
1980041
Epilepsia. 1990;31 Suppl 3:S67-73
2226373
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10955-9
1279699
Neurology. 1985 Oct;35(10):1406-14
3929158
J Biol Chem. 1973 Nov 25;248(22):7792-7
4147983
Neuron. 1996 Mar;16(3):675-86
8785064
Epilepsia. 1961 Jun;2:111-6
14453734
J Neurosurg. 1988 Mar;68(3):456-61
3343616
N Engl J Med. 1990 Aug 23;323(8):497-502
2115976
Brain Res. 1999 Nov 20;847(2):347-51
10575107
Curr Opin Cell Biol. 1997 Aug;9(4):565-72
9261059
Brain Res Mol Brain Res. 2000 Jan 10;75(1):105-12
10648893
Photochem Photobiol. 1978 Oct-Nov;28(4-5):803-9
216034
Brain Res Mol Brain Res. 1995 Oct;33(1):7-21
8774941
Arch Neurol. 1983 Jan;40(1):7-10
6848098
Neuroscience. 1992 Nov;51(2):295-310
1465194
Ann Neurol. 1978 Oct;4(4):329-36
103489
Ann N Y Acad Sci. 1999;890:301-11
10668435
Exp Neurol. 1998 Sep;153(1):123-7
9743573
Brain Res. 1991 Feb 1;540(1-2):315-8
1675918
Neurosci Lett. 1994 Oct 10;180(1):33-6
7877756
Epilepsy Res. 2000 May;39(3):201-9
10771246
Arch Biochem Biophys. 1962 Jul;98:46-8
13914231
J Lipid Res. 1966 May;7(3):341-8
5929349
Prog Neurobiol. 1992;38(3):317-34
1312245
Science. 1989 May 19;244(4906):798-800
2567056
FEBS Lett. 1973 Feb 1;29(3):205-210
11946914
Brain Res Bull. 2000 Jul 15;52(5):357-61
10922514
Fed Proc. 1973 Aug;32(8):1870-4
4352451
Psychiatry Clin Neurosci. 1995 Jun;49(3):S171-3
8612136
Epilepsia. 2000;41 Suppl 6:S195-9
10999544
Epilepsy Res. 1990 Aug;6(3):215-20
1980245
Epilepsia. 2000 Sep;41(9):1091-4
10999546
Neuron. 1994 Sep;13(3):713-25
7917301
Science. 1987 Jan 2;235(4784):66-9
3798095
J Biol Chem. 1992 Oct 15;267(29):21098-104
1400419
Ann N Y Acad Sci. 1972 Dec 18;203:4-11
4512106
Neuroreport. 1993 Apr;4(4):444-6
7684618
Chem Biol Interact. 1976 Sep;15(1):77-89
183903
J Neurol Neurosurg Psychiatry. 1975 Apr;38(4):378-81
806666
Trends Neurosci. 1991 Feb;14(2):60-7
1708538
J Neurosci. 1989 Jul;9(7):2562-74
2501460
J Neurosurg. 1971 Aug;35(2):185-91
5570780
Science. 1988 Jun 24;240(4860):1784-6
3289118
Exp Neurol. 1980 Mar;67(3):472-80
7353611
Brain Res. 1989 Jul 24;493(1):168-74
2776004
Epilepsy Res. 1993 Feb;14(2):165-73
8453952
Epilepsia. 1970 Mar;11(1):81-94
4987163
Int Rev Neurobiol. 1976;19:75-121
13046
J Neurosci. 1995 Mar;15(3 Pt 1):1835-53
7891138
Lancet. 1993 Jun 26;341(8861):1607-10
8099987
Neurochem Int. 1996 Aug;29(2):111-4
8837038
Brain Res. 1978 Aug 25;152(2):406-10
679035
Res Commun Mol Pathol Pharmacol. 1999;105(1-2):23-33
10850366
Neuroscience. 1997 May;78(2):351-9
9145792
J Neurosurg. 1983 Feb;58(2):236-41
6848681
Ann N Y Acad Sci. 1972 Dec 18;203:12-28
4572176
Epilepsy Res. 1987 Nov-Dec;1(6):313-20
3504407
Nature. 1966 Nov 5;212(5062):617
5971687
J Neurochem. 2001 Feb;76(3):892-900
11158261
Exp Neurol. 1979 Nov;66(2):205-19
114405
Neurosci Lett. 1994 Mar 28;170(1):74-6
7518894
J Neurosurg. 1999 Oct;91(4):588-92
10507379
Exp Neurol. 1984 Jan;83(1):62-70
6690325
J Neurochem. 1980 Oct;35(4):1004-7
6256498
Brain Res. 1989 Oct 30;501(1):58-65
2572307
Adv Enzymol Relat Areas Mol Biol. 1974;41(0):35-97
4371571
Epilepsia. 1954 Nov;3:49-74
13261969
J Neurochem. 1984 Apr;42(4):976-80
6699647
Neurology. 1989 Aug;39(8):1089-93
2761703
Epilepsy Behav. 2005 Dec;7 Suppl 3:S25-8
16239127
J Neurochem. 1997 Apr;68(4):1564-70
9084427
Arch Neurol. 1986 Aug;43(8):771-3
3089201
J Neurosurg. 1981 Jun;54(6):802-6
6165810
Science. 1989 Aug 18;245(4919):758-61
2549634
Epilepsy Res. 1994 May;18(1):85-8
7916288
Brain Res. 1988 Oct 25;463(1):163-7
3196905
Chin Med J (Engl). 1989 Jan;102(1):24-7
2504548
Eur J Biochem. 1968 Oct 17;6(1):126-30
4387188
J Comp Neurol. 1996 Apr 15;367(4):595-606
8731228
Brain Res. 1992 Feb 28;573(2):345-8
1354551
J Neurol Neurosurg Psychiatry. 1984 Dec;47(12):1345-7
6439825
J Mol Neurosci. 2000 Jun;14(3):183-90
10984194
Prog Neurobiol. 1994 Nov;44(4):377-96
7886231
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368-71
1648740
J Neurosci. 1995 Nov;15(11):7734-46
7472524
J Neurochem. 1994 Oct;63(4):1565-7
7523594
Acta Med Okayama. 2004 Jun;58(3):111-8
15471432
Ann Neurol. 1989 Sep;26(3):347-51
2802534