title: Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses.
abstract: 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.
authors.affiliation: Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Yi
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Guo
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.forename: Sheng-Qiang
authors.initials: SQ
authors.lastname: Chen
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liao
references.citation: Stroke. 1995 Mar;26(3):466-72
references.pmid: 7886726
references.citation: Brain Pathol. 1992 Jul;2(3):235-43
references.pmid: 1343839
references.citation: Epilepsy Res. 1992 Nov;13(2):107-12
references.pmid: 1334455
references.citation: Am J Cardiovasc Drugs. 2002;2(5):303-13
references.pmid: 14727960
references.citation: J Cereb Blood Flow Metab. 1995 Nov;15(6):948-52
references.pmid: 7593355
references.citation: J Cereb Blood Flow Metab. 1992 Jan;12(1):2-11
references.pmid: 1345757
references.citation: Brain Res. 1997 Mar 7;750(1-2):325-8
references.pmid: 9098561
references.citation: J Pediatr. 2002 Jul;141(1):31-5
references.pmid: 12091848
references.citation: Rev Neurol. 2001 Apr 16-30;32(8):714-7
references.pmid: 11391504
references.citation: Neuroreport. 2001 Jul 20;12(10):2255-8
references.pmid: 11447345
references.citation: Brain Res. 1993 May 28;612(1-2):190-9
references.pmid: 7687190
references.citation: Stroke. 1998 Nov;29(11):2363-6
references.pmid: 9804649
references.citation: Epilepsia. 1986 Sep-Oct;27(5):490-7
references.pmid: 3757936
references.citation: Int J Neuropsychopharmacol. 2008 May;11(3):321-9
references.pmid: 17897482
references.citation: J Neurosci. 1996 Aug 15;16(16):5004-13
references.pmid: 8756431
references.citation: Pediatr Neurol. 1990 Jul-Aug;6(4):219-28
references.pmid: 2169749
references.citation: Stroke. 1995 Jan;26(1):117-21; discussion 121-2
references.pmid: 7839380
references.citation: Exp Neurol. 2003 Aug;182(2):461-9
references.pmid: 12895457
references.citation: Stroke. 1999 Aug;30(8):1598-603
references.pmid: 10436107
references.citation: Stroke. 1997 Nov;28(11):2230-6; discussion 2237
references.pmid: 9368570
references.citation: Br J Pharmacol. 2000 May;130(2):242-8
references.pmid: 10807660
references.citation: Stroke. 2000 Mar;31(3):766-72; discussion 773
references.pmid: 10700517
references.citation: Fundam Clin Pharmacol. 2005 Dec;19(6):669-75
references.pmid: 16313279
references.citation: Neurobiol Dis. 2003 Feb;12(1):82-8
references.pmid: 12609492
references.citation: Ann Neurol. 1981 Feb;9(2):131-41
references.pmid: 7235629
references.citation: J Cereb Blood Flow Metab. 1993 Jan;13(1):88-97
references.pmid: 8093250
references.citation: Epilepsia. 2000 Jun;41(6):709-13
references.pmid: 10840403
references.citation: Neuroscience. 2000;95(1):89-95
references.pmid: 10619465