机构：[1]Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA[2]Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming, China外科科室神经外科神经外一科（神经外科）昆明医科大学附属第一医院[3]Department of Neurology, No.2 Hospital of Hebei Medical University, Shijiazhuang, China[4]Department of Radiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin (PTx), a G-protein blocker, is known to suppress intracellular calcium accumulation. We hypothesize that PTx can protect against stroke by blocking calcium influx. In a permanent middle cerebral artery occlusion model, PTx (1000 ng) was given intraperitoneally 30 min after inducing stroke. Magnetic Resonance Imaging of perfusion and T2-weighted brain scans were obtained to evaluate cerebral blood flow (CBF) and infarct volume. Primary neuronal culture was used to test glutamate induced excitotoxicity and calcium influx. We established a non-linear exponential curve model to minimize variations in animal cerebrovasculature. A reduction of 40-60% in relative CBF was a critical window where infarct volume started to increase as rCBF reduced. PTx showed maximal effects in reducing infarct volume at this window. In vitro studies further demonstrated PTx increased neuronal cell survival by decreasing glutamate-induced calcium influx into neurons and preventing neurons from apoptosis. PTx salvages the ischemic penumbra by blocking calcium influx. This provides us a new mechanism upon which experimental therapies can be explored to treat ischemic stroke.
基金：
Barrow Neurological Foundation (J
Shi) and National Natural Science Foundation of China (81360204,
Z Tang) and Research Foundation of the First Affiliated Hospital of
Kunming Medical University (2013BS08, Z Tang).
第一作者机构：[1]Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA[2]Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming, China[*2]Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China.
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Neurology, Barrow Neurological Institute, St Joseph’s Hospital and Medical Center, 500 W Thomas Road, Phoenix, AZ 85013, USA.[*2]Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China.
推荐引用方式(GB/T 7714)：
Tang Zhiwei,Li Shiping,Han Pengcheng,et al.Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model[J].JOURNAL OF NEUROCHEMISTRY.2015,135(5):998-1006.doi:10.1111/jnc.13359.
APA：
Tang, Zhiwei,Li, Shiping,Han, Pengcheng,Yin, Junxiang,Gan, Yan...&Shi, Jiong.(2015).Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model.JOURNAL OF NEUROCHEMISTRY,135,(5)
MLA：
Tang, Zhiwei,et al."Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model".JOURNAL OF NEUROCHEMISTRY 135..5(2015):998-1006
医学