Abstracts

For the past two years, we have been developing a method of focal brain cooling using small thermoelectric (Peltier) devices as a potential therapy for neocortical epilepsy ([italic]Ann. Neurol[/italic] 49:721,2001). While we have been quite successful in using cortical cooling to stop seizures in an acute epilepsy model in anesthetized animals, we have recognized the need to extend our results to a chronic neocortical seizure model. We have developed a unilateral modification of the cobalt wire model described by Craig and Colasanti that reliably generates recurrent, chronic seizures in rats.
After pentobarbital anesthesia, we implant a cobalt wire 1.0 mm in diameter and 1.5 mm in length into the left motor cortex, 2 mm anterior to the bregma and 2.5 mm from the midline in 9 rats. At the time of cobalt implantation, we also insert two EEG screw electrodes over both hemispheres. After recovery from anesthesia, the animals are monitored over the next 2[frac12] weeks. Formalin-fixed brains from 3 animals were also imaged using standard magnetic resonance techniques, after removal of the ferromagnetic cobalt wire. Gradient-echo and spin-echo T2-weighted, T1-weighted MDEFT, and diffusion tensor images were obtained in a 2.5 cm birdcage RF coil in a 4.7 Tesla Oxford/Varian horizontal animal imager (resolution 234 x 234 x 1000 mM).
We have observed three seizure types. Over two weeks, 9 animals had an average of 97.2 [plusmn] 43.3 [italic]simple partial seizures[/italic] with contralateral clonic jerks, lasting 17.9 [plusmn] 46.4 minutes. These seizures, characterized by repetitive single spikes, are very evident one week after cobalt implantation, sometimes occurring over 17 times per day. The animals had, on average, 28.9 [plusmn] 11.9 [italic] secondary generalized seizures[/italic], lasting 34.5 [plusmn] 19 seconds. These seizures arise 3-5 times per day. A subset of 4 animals each had 28.5 [plusmn] 27.5 [italic]subclinical seizures[/italic] with a paroxysmal EEG, lasting 40.9 [plusmn] 56.8 sec. There was loss of the MR signal, indicating spread of the ferromagnetic cobalt into the brain tissue. The image disruption caused by the cobalt was quite abrupt, indicating a sharp cobalt concentration gradient. The lack of anatomic differences in the white or gray matter outside the areas masked by the cobalt suggest no widespread cerebral injury. We were able to detect these seizures using a Fast Fourier Transform based computer algorithm that had already been tested in our acute seizure models.
The unilateral cobalt wire model generates focal cortical seizures that are less frequent than those seen in our acute model, but persist for up to 2 weeks. The ferromagnetic signal present even after wire removal indicates that metallic cobalt leaches into the cortex and may be responsible for generating the seizures. This model should be useful for testing new therapies for neocortical epilepsy.
[Supported by: Citizens United for Research in Epilepsy (CURE), McDonnell Center for Higher Brain Function, and the NIH (R01 NS 37773 and R01 NS 42936)]