Neuroprotection by lamotrigine in a rat model of neonatal hypoxic-ischaemic encephalopathy.
Hypoxic-ischaemic (HI) encephalopathy is a severe complication of perinatal asphyxia and remains a frequent cause of a variety of brain disorders with long-term effects on the patients' life. The associated brain damage is strongly related to the toxic action of excitatory amino acids, especially glutamate and aspartate. Lamotrigine is an anti-epileptic drug that blocks the voltage-gated sodium channels of the presynaptic neuron and inhibits the release of glutamate. In the present study a well-established model of perinatal asphyxia in 7-d-old rats was used to investigate the effect of lamotrigine on HI-induced damage to different hippocampal brain structures, since disruption of this brain area is thought to play a key role in schizophrenia and epilepsy. Therefore, a combination of ischaemia, induced by unilateral occlusion of the left common carotid artery, followed by exposure to a 1-h period of hypoxia, was carried out in neonatal 7-d-old rats. Immediately after the insult, lamotrigine was given i.p. The histological outcome in the hippocampus was conducted and the tissue levels of glutamate, aspartate, GABA, and glutamine in the same area were determined. A remarkable reduction of HI-evoked damaged neurons in most of the investigated hippocampal regions was noted after lamotrigine administration. Furthermore, lamotrigine decreased the asphyxia-induced hippocampal tissue levels of glutamate and aspartate. Immediately after perinatal asphyxia GABA levels were enhanced, while levels of glutamine were decreased. Lamotrigine administration did not affect either GABA or glutamine levels. These results suggest a neuroprotective effect of lamotrigine in this particular animal model of neonatal HI encephalopathy.
Papazisis
Georgios
G
Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Kallaras
Konstantinos
K
Kaiki-Astara
Anastasia
A
Pourzitaki
Chrysa
C
Tzachanis
Dimitrios
D
Dagklis
Themistoklis
T
Kouvelas
Dimitrios
D
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D000077213:Lamotrigine; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014227:Triazines / Q000627:therapeutic use*
D000596:Amino Acids; D018696:Neuroprotective Agents; D014227:Triazines; D000077213:Lamotrigine