Neuroprotective Role of Lamotrigine in Pilocarpine Induced Status Epilepticus Model
Abstract number :
1.140
Submission category :
Year :
2000
Submission ID :
3155
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Steven C R Williams, B S Meldrum, Gerard D Pratt, J C Barnes, L A Lynch, Institute of Psychiatry, Denmark Hill, London, United Kingdom; Institute of Psychiatry, London, United Kingdom; Glaxo Wellcome R&D, Stevenage, United Kingdom; Glaxo Wellcome R&D, Ste
RATIONALE: Lamotrigine (LTG) is an established anti-epileptic agent that blocks voltage-dependant sodium channels, thereby preventing excitatory neurotransmitter release. We hypothesised that a dose of lamotrigine given after onset of status epilepticus may reduce the extent of cell damage caused by status in the pilocarpine model. Previous Magnetic Resonance Imaging studies have outlined apparent diffusion coefficient (ADC) and T2 abnormalities in post-seizure brain tissue across an extensive temporal range; the current study has investigated the effect of lamotrigine on these parameters. METHODS:_18 male Wistar rats were injected with pilocarpine (380mg/kg i.p.), preceded by N-methyl scopolamine (1mg/kg i.p.). 9 animals received no further treatment, while 9, having experienced 20 minutes of status, were given LTG (30mg/kg i.p). Gaussian-weighted images were reconstructed from the data and ADC and T2 maps were calculated from the T2/T2 diffusion-weighted images and the PD/T2 weighted pairs of images, respectively. RESULTS: Administration of LTG seemed to have little effect on the duration of limbic status during three hours of observation however, LTG-treated animals appeared to experience fewer generalised tonic-clonic convulsions. The mean ADC was significantly lower in the pilocarpine only group (57.5% of control value) at 24 hours post-status. Mean ADC was also lowered in the pilocarpine + LTG group, although significantly higher than that seen in the pilocarpine group (77.2% of control value). The mean T2 value in the pilocarpine only group was significantly higher than the control group, 24 hours post-status. Again, the value for the pilocarpine + LTG was significantly lower than that of the pilocarpine group. CONCLUSIONS: LTG appears to play a neuroprotective role 24 hours following pilocarpine injection. Reduction in ADC, a common observation often associated with cytotoxic oedema and cell swelling is shown to be less severe in the piriform cortex following LTG administration. Increase in T2, which is often a marker for vasogenic oedema, was also shown to be less severe in those pilocarpine animals treated with LTG.