Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses.
Lamotrigine (LTG), an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen). LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and neuron-specific enolase (NSE) immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI) model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.
Yi
Yong-Hong
YH
Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital.
Guo
Wen-Chao
WC
Sun
Wei-Wen
WW
Su
Tao
T
Lin
Han
H
Chen
Sheng-Qiang
SQ
Deng
Wen-Yi
WY
Zhou
Wei
W
Liao
Wei-Ping
WP
Stroke. 1995 Mar;26(3):466-72
7886726
Brain Pathol. 1992 Jul;2(3):235-43
1343839
Epilepsy Res. 1992 Nov;13(2):107-12
1334455
Am J Cardiovasc Drugs. 2002;2(5):303-13
14727960
J Cereb Blood Flow Metab. 1995 Nov;15(6):948-52
7593355
J Cereb Blood Flow Metab. 1992 Jan;12(1):2-11
1345757
Brain Res. 1997 Mar 7;750(1-2):325-8
9098561
J Pediatr. 2002 Jul;141(1):31-5
12091848
Rev Neurol. 2001 Apr 16-30;32(8):714-7
11391504
Neuroreport. 2001 Jul 20;12(10):2255-8
11447345
Brain Res. 1993 May 28;612(1-2):190-9
7687190
Stroke. 1998 Nov;29(11):2363-6
9804649
Epilepsia. 1986 Sep-Oct;27(5):490-7
3757936
Int J Neuropsychopharmacol. 2008 May;11(3):321-9
17897482
J Neurosci. 1996 Aug 15;16(16):5004-13
8756431
Pediatr Neurol. 1990 Jul-Aug;6(4):219-28
2169749
Stroke. 1995 Jan;26(1):117-21; discussion 121-2
7839380
Exp Neurol. 2003 Aug;182(2):461-9
12895457
Stroke. 1999 Aug;30(8):1598-603
10436107
Stroke. 1997 Nov;28(11):2230-6; discussion 2237
9368570
Br J Pharmacol. 2000 May;130(2):242-8
10807660
Stroke. 2000 Mar;31(3):766-72; discussion 773
10700517
Fundam Clin Pharmacol. 2005 Dec;19(6):669-75
16313279
Neurobiol Dis. 2003 Feb;12(1):82-8
12609492
Ann Neurol. 1981 Feb;9(2):131-41
7235629
J Cereb Blood Flow Metab. 1993 Jan;13(1):88-97
8093250
Epilepsia. 2000 Jun;41(6):709-13
10840403
Neuroscience. 2000;95(1):89-95
10619465