Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

Yong-Hong Yi¹, Wen-Chao Guo¹, Wei-Wen Sun¹, Tao Su¹, Han Lin¹, Sheng-Qiang Chen¹, Wen-Yi Deng¹, Wei Zhou², Wei-Ping Liao¹

¹Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, ²Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. China

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.

Keywords: hypoxic-ischemic brain damage, lamotrigine, neonatal rat, neuroprotection