Gáll Zsolt, Kelemen Krisztina, Tolokán Andrea, Zolcseak István, Sável István, Bod Réka, Ferencz Elek, Vancea Szende, Urkon Melinda, Kolcsár Melinda
Department of Pharmacology and Clinical Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mureș, Romania.
Department of Physiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mureș, Romania.
Biomedicines. 2022 Jul 28;10(8):1811. doi: 10.3390/biomedicines10081811.
Cannabidiol (CBD) showed anticonvulsant action in several preclinical models and is currently approved by regulatory agencies to treat childhood epilepsy syndromes. However, CBD treatment has limited benefits, and its long-term effects on cognition are not fully understood yet. This study aimed to examine the impact of long-term CBD treatment in the pentylenetetrazole (PTZ)-kindling model of epilepsy. Adult male Wistar rats ( = 24) received PTZ (35 mg/kg intraperitoneally) every other day until two consecutive generalized seizures occurred. CBD (60 mg/kg body weight) was administered daily by the oral route until the kindled state was achieved ( = 12). To confirm that the formulation and administration techniques were not of concern, liquid chromatography-mass spectrometry was performed to test the brain penetration of the CBD formula. As a result of CBD treatment, a lower mortality rate and significantly prolonged generalized seizure latency (925.3 ± 120.0 vs. 550.1 ± 69.62 s) were observed, while the frequency and duration of generalized seizures were not influenced. The CBD-treated group showed a significant decrease in vertical exploration in the open field test and a significant decrease in the discrimination index in the novel object recognition (NOR) test (-0.01 ± 0.17 vs. 0.57 ± 0.15, = 0.04). The observed behavioral characteristics may be connected to the decreased thickness of the stratum pyramidale or the decreased astrogliosis observed in the hippocampus. In conclusion, CBD treatment did not prevent kindling, nor did it affect seizure frequency or duration. However, it did increase the latency to the first seizure and decreased the prolonged status epilepticus-related mortality in PTZ-kindled rats. The cognitive impairment observed in the NOR test may be related to the high dose used in this study, which may warrant further investigation.
大麻二酚（CBD）在多种临床前模型中显示出抗惊厥作用，目前已获监管机构批准用于治疗儿童癫痫综合征。然而，CBD治疗的益处有限，其对认知的长期影响尚未完全明确。本研究旨在探讨长期CBD治疗对癫痫戊四氮（PTZ）点燃模型的影响。成年雄性Wistar大鼠（n = 24）每隔一天腹腔注射PTZ（35 mg/kg），直至连续出现两次全身性惊厥。每天经口给予CBD（60 mg/kg体重），直至达到点燃状态（n = 12）。为确认制剂和给药技术无关紧要，采用液相色谱 - 质谱法检测CBD制剂的脑渗透性。CBD治疗的结果显示，死亡率降低，全身性惊厥潜伏期显著延长（925.3 ± 120.0 vs. 550.1 ± 69.62秒），而全身性惊厥的频率和持续时间未受影响。CBD治疗组在旷场试验中的垂直探索显著减少，在新物体识别（NOR）试验中的辨别指数显著降低（-0.01 ± 0.17 vs. 0.57 ± 0.15，P = 0.04）。观察到的行为特征可能与海马体中锥体层厚度降低或星形胶质细胞增生减少有关。总之，CBD治疗不能预防点燃，也不影响癫痫发作频率或持续时间。然而，它确实增加了首次发作的潜伏期，并降低了PTZ点燃大鼠中与癫痫持续状态延长相关的死亡率。在NOR试验中观察到的认知障碍可能与本研究中使用的高剂量有关，这可能值得进一步研究。
