Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Epilepsia. 2010 Sep;51(9):1721-8. doi: 10.1111/j.1528-1167.2010.02700.x. Epub 2010 Aug 17.
Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic 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 antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy.
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 (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 μl/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period.
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 nonconvulsive 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.
This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures.
尽管对于耐药性癫痫患者有多种治疗选择，如癫痫手术和神经刺激，但许多患者仍有癫痫发作和/或与药物相关的脑和全身副作用。局部脑内递送电痉挛化合物可能是一种具有特定优势的新策略，例如选择更高的局部剂量和减少副作用。在这项研究中，我们评估了在海人酸大鼠模型（颞叶癫痫的验证模型）中局部递送电痉挛化合物的抗癫痫作用。
15 只大鼠在腹腔内注射海人酸后诱发自发性癫痫发作，在双侧海马体内植入深度电极和套管。套管与渗透微型泵相连，以允许持续的海马内递药。大鼠在自由移动的情况下通过视频-脑电图（EEG）进行永久监测。在局部海马内递送生理盐水（基线）的 2 周期间对癫痫发作进行评分，随后进行 2 周的局部腺苷（6mg/ml）（n=10）或生理盐水（n=5）（0.23μl/h）（治疗）。在 10 只腺苷治疗大鼠中的 7 只，在洗脱期也递送生理盐水。
在治疗期间，与基线率相比，腺苷治疗组大鼠的每日平均癫痫发作频率降低了 33%（p<0.01）。4 只大鼠的癫痫发作频率降低了至少 50%。非惊厥性和惊厥性癫痫发作在治疗期间均显著减少。在生理盐水对照组中，治疗期间大鼠的每日平均癫痫发作频率增加了 35%。
本研究证明了在有自发性癫痫发作的大鼠中，持续递送电腺苷具有抗癫痫作用。
