Jacobs School of Medicine and Biomedical Sciences, Buffalo Medical Center, University at Buffalo, 100 High St, Buffalo, NY, 14203, USA.
Department of Primary Care, University of Zurich, Zurich, Switzerland.
Transl Stroke Res. 2020 Apr;11(2):165-184. doi: 10.1007/s12975-019-00718-7. Epub 2019 Jul 20.
Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the cardiovascular sympathetic autonomic dysfunction, presented in part as the by-product of the ischemic damage to the noradrenergic centers of the brain. Unlike high levels in the plasma, the brain may face suboptimal levels of norepinephrine (NE), with adverse effects on the clinical and functional outcomes of ischemic stroke. The intravenous administration of NE and other sympathomimetic agents, in an attempt to increase cerebral perfusion pressure, often aggravates the ischemia-induced rise in blood pressure (BP) with life-threatening consequences for stroke patients, the majority of whom present with hypertension at the time of admission. Unlike the systemic administration, the central administration of NE reduces BP while exerting anti-inflammatory and neuroprotective effects. These characteristics of centrally administered NE, combined with the short latency of response, make it an ideal candidate for use in the acute phase of stroke, followed by the use of centrally acting noradrenergic agonists, such as NE reuptake inhibitors and B2-adrenergic receptor agonists for stroke rehabilitation. In addition, a number of nonpharmacological strategies, such as transcutaneous vagus nerve stimulation (tVNS) and trigeminal nerve stimulation (TNS), have the potential to enhance the central noradrenergic functional activities and improve stroke clinical outcomes. Many factors could influence the efficacy of the noradrenergic treatment in stroke patients. These factors include the type of the noradrenergic agent; the dose, frequency, and duration of administration; the timing of administration in relation to the acute event; and the site and characteristics of the ischemic lesions. Having this knowledge, combined with the better understanding of the regulation of noradrenergic receptors in different parts of the brain, would pave the path for the successful use of the centrally acting noradrenergic agents in the management of ischemic stroke.
缺血性中风是全球发病率和死亡率的主要原因，给人类健康带来了巨大负担，而且治疗选择有限。缺血性中风的短期和长期影响之一是心血管交感自主神经功能障碍，部分表现为大脑去甲肾上腺素能中枢缺血损伤的副产品。与血浆中高水平的去甲肾上腺素（NE）不同，大脑可能面临去甲肾上腺素水平不足的情况，这对缺血性中风的临床和功能结局产生不利影响。静脉内给予 NE 和其他拟交感胺类药物以试图增加脑灌注压，往往会加重缺血引起的血压升高（BP），对中风患者造成危及生命的后果，其中大多数患者在入院时就患有高血压。与全身给药不同，中枢给药 NE 可降低血压，同时发挥抗炎和神经保护作用。中枢给药 NE 的这些特性，加上其反应潜伏期短，使其成为中风急性期应用的理想候选药物，随后可使用中枢作用去甲肾上腺素能激动剂，如去甲肾上腺素再摄取抑制剂和 B2-肾上腺素能受体激动剂，用于中风康复。此外，许多非药物策略，如经皮迷走神经刺激（tVNS）和三叉神经刺激（TNS），具有增强中枢去甲肾上腺素能功能活动和改善中风临床结局的潜力。许多因素可能会影响中风患者的去甲肾上腺素治疗效果。这些因素包括去甲肾上腺素能药物的类型；给药的剂量、频率和持续时间；与急性事件相关的给药时间；以及缺血性病变的部位和特征。了解这些知识，并更好地了解大脑不同部位去甲肾上腺素受体的调节，将为成功使用中枢作用去甲肾上腺素能药物治疗缺血性中风铺平道路。
