Bilateral Anterior Thalamic Nucleus Lesions Are Not Protective against Seizures in Chronic Pilocarpine Epileptic Rats

Abstract

Aims: To investigate whether anterior thalamic nucleus (AN) lesions are protective against spontaneous recurrent seizures in the chronic phase of the pilocarpine model of epilepsy. Methods: Two groups of rats were treated with bilateral AN radiofrequency thalamotomies or sham surgery 2 weeks after pilocarpine-induced status epilepticus. After the lesions, animals were videotaped from the 2nd to the 8th week after status epilepticus (total 180 h). Results: During the 6 weeks of observation, no differences in the frequency of spontaneous seizures were found between animals that had bilateral AN lesions (n = 26; 3.1 ± 0.6 seizures per animal) and controls (n = 25; 3.0 ± 0.6 seizures per animal; p = 0.8). Conclusions: We conclude that AN thalamotomies were not effective in reducing the frequency of seizures during the chronic phase of the pilocarpine model of epilepsy.

Microinjection of GABAergic agents into the anterior nucleus of the thalamus modulates pilocarpine-induced seizures and status epilepticus

“…So far, the only therapy capable of hindering these events in our series of experiments in the pilocarpine model of epilepsy was AN thalamotomy. 2 This treatment however, did not lead to a significant reduction in seizure frequency in chronic epileptic animals 34 and is known to cause significant memory disturbance. 14,15 Additional investigation to characterize suitable treatment modalities to prevent/block seizure activity with limited adverse effects is still necessary.…”

The potential of brain stimulation in status epilepticus

“…The use of deep brain stimulation has not been reported extensively in status epilepticus but it is mentioned in discussions (see for example Robakis & Hirsch, 2006). Data from animal seizure models have indicated that low or high frequency stimulation of the anterior thalamic nucleus can increase seizure threshold and delay the occurrence of status epilepticus following administration of the convulsant pilocarpine (Hamani et al., 2009). However, the same stimulation protocol did not terminate established status epilepticus, indicating that the mechanisms underlying induction and maintenance of status epilepticus differ (Hamani et al., 2009).…”

Dopamine mechanisms in learning and memory: evidence from rodent studies

“…Interestingly, electrical stimulation of the ANT was found effective for treating refractory focal epilepsy in a clinical trial , while memory problems were reported as adverse effects (Fisher et al, 2010), which may be in part due to its central connectivity (Child & Benarroch, 2013). In line with the finding from these studies, memory improvement was observed in rats stimulated in the EC during behavioral studies , while memory impairments were retained in rats stimulated in the ANT (Hamani, et al, 2009). DBS effects in the MTT and memory are still unknown.…”

“…This seems to be in line with behavioral findings of our unpublished data and previous studies. DBS into the EC reversed the effects of memory loss caused by scopolamine, while DBS into the ANT had memory loss retention (Hamani et al, 2009). It is suspected that the neurons in the VTA had a phenotypic switching from GABA cells to TH cells caused by the environmental factor of DBS into the ANT, but not by DBS in the EC or MTT.…”