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Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

Annelies Van Dycke (UGent) , Robrecht Raedt (UGent) , Ine Dauwe (UGent) , Tom Sante (UGent) , Tine Wyckhuys (UGent) , Alfred Meurs (UGent) , Kristl Vonck (UGent) , Wytse Wadman (UGent) and Paul Boon (UGent)
(2010) EPILEPSIA. 51(9). p.1721-1728
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Abstract
Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still suffer from seizures and/or drug related cerebral and systemic side effects. Local intracerebral delivery of anti-epileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the anti-epileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods: Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG. Seizures were scored during two weeks of local hippocampal delivery of saline (baseline), followed by two weeks of local adenosine (6mg/ml) (n=10) or saline (n=5) delivery (0.23µl/h) (treatment). In 7/10 adenosine-treated rats, saline was also delivered during a washout period. Results: During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p<0.01). Four rats had a seizure frequency reduction of at least 50%. Both non-convulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions: This study demonstrates the anti-seizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures.
Keywords
SUPPRESSION, HIPPOCAMPUS, RELEASE, RECEPTORS, GENE THERAPIES, BRAIN IMPLANTS, KINDLED SEIZURES, REFRACTORY EPILEPSY, STEM-CELL GRAFTS, TEMPORAL-LOBE EPILEPSY, Epilepsy, Adenosine, Local delivery, Intrahippocampal, Spontaneous seizures, Kainic acid

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Chicago
Van Dycke, Annelies, Robrecht Raedt, INE DAUWE, TOM SANTE, Tine Wyckhuys, Alfred Meurs, Kristl Vonck, Wytse Wadman, and Paul Boon. 2010. “Continuous Local Intrahippocampal Delivery of Adenosine Reduces Seizure Frequency in Rats with Spontaneous Seizures.” Epilepsia 51 (9): 1721–1728.
APA
Van Dycke, A., Raedt, R., DAUWE, I., SANTE, T., Wyckhuys, T., Meurs, A., Vonck, K., et al. (2010). Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures. EPILEPSIA, 51(9), 1721–1728.
Vancouver
1.
Van Dycke A, Raedt R, DAUWE I, SANTE T, Wyckhuys T, Meurs A, et al. Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures. EPILEPSIA. 2010;51(9):1721–8.
MLA
Van Dycke, Annelies, Robrecht Raedt, INE DAUWE, et al. “Continuous Local Intrahippocampal Delivery of Adenosine Reduces Seizure Frequency in Rats with Spontaneous Seizures.” EPILEPSIA 51.9 (2010): 1721–1728. Print.
@article{958967,
  abstract     = {Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still suffer from seizures and/or drug related cerebral and systemic side effects. Local intracerebral delivery of anti-epileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the anti-epileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy.
Methods: Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG. Seizures were scored during two weeks of local hippocampal delivery of saline (baseline), followed by two weeks of local adenosine (6mg/ml) (n=10) or saline (n=5) delivery (0.23{\textmu}l/h) (treatment). In 7/10 adenosine-treated rats, saline was also delivered during a washout period.
Results: During the treatment period a mean daily seizure frequency reduction of 33\% compared to the baseline rate was found in adenosine-treated rats (p{\textlangle}0.01). Four rats had a seizure frequency reduction of at least 50\%. Both non-convulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35\% during the treatment period.
Conclusions: This study demonstrates the anti-seizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures.},
  author       = {Van Dycke, Annelies and Raedt, Robrecht and Dauwe, Ine and Sante, Tom and Wyckhuys, Tine and Meurs, Alfred and Vonck, Kristl and Wadman, Wytse and Boon, Paul},
  issn         = {0013-9580},
  journal      = {EPILEPSIA},
  language     = {eng},
  number       = {9},
  pages        = {1721--1728},
  title        = {Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures},
  url          = {http://dx.doi.org/10.1111/j.1528-1167.2010.02700.x},
  volume       = {51},
  year         = {2010},
}

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