Lamotrigine attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits

• Published in: Surgical neurology 2008-10, Vol.70 (4), p.344-351
• Main Authors: Seçkin, Hakan, MD, PhD, Yigitkanli, Kazim, MD, Besalti, Omer, PhD, Kosemehmetoglu, Kemal, MD, Ozturk, Evrim, MD, Simsek, Serkan, MD, Belen, Deniz, MD, Bavbek, Murad, MD
• Format: Article
• Language: English
• Subjects: Animals; Basilar Artery - pathology; Calcium Channels - physiology; Disease Models, Animal; Excitatory Amino Acid Antagonists - pharmacology; Hippocampus - pathology; Lamotrigine; Male; Neurology; Rabbit; Rabbits; Severity of Illness Index; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - drug therapy; Subarachnoid Hemorrhage - pathology; Surgery; Triazines - pharmacology; Vasospasm; Vasospasm, Intracranial - drug therapy; Vasospasm, Intracranial - pathology; Vertebrobasilar Insufficiency - drug therapy; Vertebrobasilar Insufficiency - pathology
• ISSN: 0090-3019; 1879-3339
• DOI: 10.1016/j.surneu.2007.07.052

Abstract Background Increasing evidence implicates voltage-dependent sodium and potassium channels, in addition to calcium channels of various types, in the pathophysiological development of cerebral vasospasm. This study investigated the ability of LTG, an antiepileptic drug with multi-ion channel inhibition properties, to prevent cerebral vasospasm and subsequent neural ischemia in a rabbit model of SAH. Methods Thirty-five New Zealand white rabbits were assigned to 1 of 3 groups: (1) control (no SAH, saline injection); (2) SAH alone; (3) SAH + LTG, 20 mg/kg daily. Animals were killed 72 hours after SAH, then basilar artery lumen areas and arterial wall thickness were measured in all groups. The histological sections of the CA1 and CA3 regions and dentate gyri of the hippocampi were evaluated semiquantitatively for neural tissue degeneration. Results In the SAH group, the mean luminal cross-sectional area of the basilar artery was reduced by 62% after SAH as compared with the non-SAH controls ( P < .0001). After SAH, the vasospastic response was attenuated by 36% in animals treated with 20 mg/kg of LTG compared with the SAH group ( P < .005). The mean luminal cross-sectional areas of the basilar artery were 279 000 ± 27 000 μ m2 in the control group, 173 000 ± 17 600 μ m2 in the SAH group, and 236 000 ± 10 000 μ m2 in the SAH + LTG group. The differences between the SAH group and the LTG-treated group were statistically significant ( P < .0001). Histological examination was done in 12 control, 12 SAH, and 9 SAH + LTG–treated animals. The mean degeneration score for the control group and SAH + LTG group was statistically significant ( P = .012). The difference between the SAH group and SAH+ LTG group was also statistically significant ( P = .006). Conclusions These findings demonstrate that oral administration of LTG has marked neuroprotective effect and significantly attenuates cerebral vasospasm after SAH, thus providing additional support for the role of non–L-type calcium channels and voltage-dependent sodium channels in vasospasm.