scholarly journals Anticonvulsant Effects by Bilateral and Unilateral Transplantation of GABA-Producing Cells into the Subthalamic Nucleus in an Acute Seizure Model

2014 ◽  
Vol 23 (1) ◽  
pp. 111-132 ◽  
Author(s):  
Annelie Handreck ◽  
Bianca Backofen-Wehrhahn ◽  
Sonja Bröer ◽  
Wolfgang Löscher ◽  
Manuela Gernert
Author(s):  
Malte Feja ◽  
Lillian S. Deking ◽  
Manuela Gernert

Aims : Intracerebral drug delivery is an emerging strategy for the treatment of refractory epilepsies. Recently, the GABA A receptor agonist muscimol was infused into the epileptic focus in drug-resistant epilepsy patients (Heiss et al. 2019 Neurosurgery). In seizure and epilepsy models in rats, muscimol has shown anticonvulsant potential when injected acutely into the subthalamic nucleus (STN). However, continuous administration would be required for the clinical setting. Thus, we hypothesized that chronic convection-enhanced muscimol delivery into the STN produces anticonvulsant effects in an acute rat seizure model. Methods : We examined the effects of intra-STN muscimol following a single microinjection (30 and 60 ng/250 nl) and during continuous administration via a microinfusion pump (60 and 600 ng/day over 3 weeks) on the seizure threshold of female Wistar Unilever rats. Timed intravenous pentylenetetrazole (PTZ) infusion was used as an acute seizure test particularly sensitive to GABA-potentiating manipulations. Results : Acute STN muscimol infusion significantly increased PTZ seizure thresholds compared to vehicle-injected animals. The anticonvulsant effect persisted in the first week during chronic STN inhibition and diminished in the second week, indicating tolerance. Low doses of muscimol were well tolerated and not associated with behavioral adverse effects (e.g., sedation, circling) observed after infusion of higher doses. Evaluation of the spatial distribution of BODIPY-labeled muscimol revealed behavioral adverse effects may be attributable to drug spread into adjacent regions of the STN. Conclusions : These results substantiate the STN as a key region in seizure control and indicate the potential of chronic targeted muscimol delivery for prolonged anticonvulsant effects.


2017 ◽  
Vol 32 (4) ◽  
pp. 1051-1060 ◽  
Author(s):  
Itefaq Hussain Qureshi ◽  
Azra Riaz ◽  
Rafeeq Alam Khan ◽  
Afaq Ahmed Siddiqui

2018 ◽  
Vol 310 ◽  
pp. 70-83 ◽  
Author(s):  
Bianca Backofen-Wehrhahn ◽  
Laura Gey ◽  
Sonja Bröer ◽  
Björn Petersen ◽  
Miriam Schiff ◽  
...  

2012 ◽  
Vol 46 (2) ◽  
pp. 362-376 ◽  
Author(s):  
Sonja Bröer ◽  
Bianca Backofen-Wehrhahn ◽  
Marion Bankstahl ◽  
Laura Gey ◽  
Manuela Gernert ◽  
...  

2015 ◽  
Vol 26 (1) ◽  
pp. 82-87

The aim of this study was to characterize the anticonvulsant effects of levetiracetam (LEV) in combination with lamotrigine (LTG – a second-generation antiepileptic drug), in the mouse 6 Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to characterize the consequent anticonvulsant interactions between the drug combinations. Results indicated that LEV administered singly was associated with a DRRC that was parallel to that for LTG. With isobolography for parallel DRRCs, the combination of LEV with LTG at three fixed-ratios of 1:3, 1:1 and 3:1 exerted additive interaction. LEV combined with LTG exerted additive interaction in the mouse 6 Hz psychomotor seizure model.


2020 ◽  
Vol 12 (4) ◽  
pp. 84-90
Author(s):  
O. A. Gromova ◽  
V. I. Demidov ◽  
A. G. Kalacheva ◽  
I. Yu. Torshin ◽  
T. R. Grishina ◽  
...  

Objective: to investigate the effect of dexketoprofen on the severity of seizures on a rat model of primary generalized seizures caused by thiosemicarbazide; to evaluate the neuroprotective effect of the drug.Material and methods. The investigation was conducted on 72 male albino rats weighing 200–300 g. The animals were given dexketoprofen and/or comparison drugs (gabapentin, sodium valproate) for 5 days, after which the seizure model was reproduced. The effects of the drugs were evaluated from a set of neurological tests and the results of a histopathological examination of the brain.Results and discussion. Dexketoprofen reduced the severity, duration, and number of primary generalized seizures and potentiated the anticonvulsant effects of gabapentin and sodium valproate. Histopathological and morphometric examinations of the rat brain showed that dexketoprofen inhibited the formation of irreversible neuronal changes (27.2%; control, 55.7%), by transferring them into reversible changes (47.7%; control, 21.8%).Conclusion. The investigation made it possible to conclude that dexketoprofen had a moderate neuroprotective effect neurologically and morphometrically verified.


2015 ◽  
Vol 28 (3) ◽  
pp. 204-207 ◽  
Author(s):  
Aleksandra Wlaz ◽  
Maria W. Kondrat-Wrobel ◽  
Katarzyna Zaluska ◽  
Ewelina Kochman ◽  
Anna R. Rekas ◽  
...  

Abstract This study was aimed at characterizing the anticonvulsant effects of levetiracetam in combination with gabapentin, in the mouse 6 Hz psychomotor seizure model. Herein, psychomotor seizures were evoked in male albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Type II isobolographic analysis was used to characterize the anticonvulsant interactions between the drugs in combination, for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. The type II isobolographic analysis revealed that the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.05) in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive in the mouse 6 Hz psychomotor seizure model. We conclude that, as the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 exerted supra-additive (synergistic) interaction in the mouse 6 Hz psychomotor seizure model, this may be considered as particularly favorable combinations in further clinical practice.


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