Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Greece.
Metab Brain Dis. 2012 Jun;27(2):221-5. doi: 10.1007/s11011-012-9301-2. Epub 2012 Apr 4.
Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.
自发性脑出血 (ICH) 占所有中风的 10-15%。尽管发病率、发病率和死亡率很高，但自发性 ICH 的精确病理生理学尚未完全了解，而关于血肿形成后主要损伤的机制的数据很少。除了作为神经递质系统的巨大重要性外，胆碱能系统似乎在脑损伤恢复中也起着重要作用。最近有人提出，大脑具有胆碱能抗炎途径，可对抗 ICH 后的炎症反应，从而限制对大脑本身的损伤。我们在此报告了我们在自发性 ICH 猪模型中关于乙酰胆碱酯酶 (AChE；一种参与胆碱能神经传递的关键膜结合酶) 作用的研究结果，重点关注损伤诱导后 4 小时和 24 小时，同时研究了 Lazaroid 抗氧化剂 U-74389G 给药的效果。我们的研究表明，U-74389G 给药后 AChE 活性被激活。Lazaroid U-74389G 似乎是一种已确立的神经保护剂，这是其在增强对 ICH 诱导的胆碱能反应中的支持作用的首次报道。
