Subtypes of anterior circulation large artery occlusions with acute brain ischemic stroke.

Anterior circulation large artery occlusion (AC-LAO) related acute ischemic stroke (AIS) is particularly common in clinics in China. We retrospectively analyzed 787 consecutively hospitalized AIS patients with AC-LAO in Hebei Province, China. AC-LAO was defined as a complete occlusion of at least one intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) based on computed tomography or magnetic resonance angiography. Among eight subtypes of AC-LAO, unilateral MCA occlusion is the most common one (49.8%, n = 392), while bilateral ICA/unilateral MCA occlusion is the least (0.3%, n = 2). Compared with unilateral MCA and unilateral ICA occlusion, patients with tandem ICA/MCA and bilateral ICA/MCA occlusion had poor outcomes after suffering AIS. Age (OR 1.022; 95%CI, 1.007 to 1.036) was an independent risk factor for single artery progressed to multiple artery occlusion, while ApoA1 (OR 0.453; 95% CI, 0.235 to 0.953) was a protective factor. Patients with unilateral MCA occlusion were prone to artery-to-artery embolism infarction subtype, unilateral ICA occlusion group were the most vulnerable to hypoperfusion/impaired emboli clearance subtype. Our results suggested various AC-LAO subtypes have different clinical characteristics and prognosis and were prone to different subtypes of infarction. Customized preventive measures based on AC-LAO subtypes may be more targeted preventions of stroke recurrences for AIS patients and could improve their prognoses.

The relationship between oxidized low-density lipoprotein and related ratio and acute cerebral infarction.

This study aimed to study the value of oxidized low-density lipoprotein (OX-LDL) and related ratio in the diagnosis of acute cerebral infarction and the classification of acute cerebral infarction.Of the 129 patients enrolled in this study, 94 patients with acute cerebral infarction were assigned to the case group, and 35 healthy subjects were enrolled as control group (n = 35). And then the case group were divided into large-artery atherosclerosis (LAA) group (n = 61) and small-artery occlusion (SAO) group (n = 33) according to the TOAST classification standard. Plasma OX-LDL levels were determined by enzyme-linked immunosorbent assay. OX-LDL/total cholesterol (OX-LDL/TC), OX-LDL/high-density lipoprotein (OX-LDL/HDL), OX-LDL/LDL were calculated.There were significant differences in OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL in patients with acute cerebral infarction and those in control group (P < .001). The area under the receiver-operating characteristic curve of OX-LDL and related ratio was >0.7 (P < .001). There was a slight positive correlation between OX-LDL/TC and National Institutes of Health Stroke Scale score at admission (r = 0.265, P = .039) in the LAA group.OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL were closely related to acute cerebral infarction, especially with large atherosclerotic cerebral infarction. OX-LDL/TC can reflect the severity of acute cerebral infarction for LAA, but it cannot predict the short-term prognosis of acute cerebral infarction.

Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice.

BACKGROUND: Oxidative damage plays a pivotal role in the pathogenesis of cerebral ischemic stroke and may represent a target for treatment. Our previous studies have proved that nuclear factor E2-related factor 2 (Nrf2) and its downstream genes served as a key mechanism for protection against oxidative stress. Paeonol (PN) is reputed to possess a broad range of therapeutic properties probably by virtue of its antioxidative ability. However little is elucidated regarding the underlying mechanisms in ischemic stroke. The aim of this study was to explore PNs effect in ischemic injury and the role of the pAkt, Nrf2 and hemeoxygenase-1 (HO-1) in the mice brains of permanent middle cerebral artery occlusion (pMCAO). METHODS: Male CD-1 mice were subjected to pMCAO and randomly divided into five groups: Sham (sham-operated+0.9% saline), pMCAO (pMCAO+0.9% saline), Vehicle (pMCAO+vehicle), PN-L (pMCAO+PN 30 mg/kg) and PN-H (pMCAO+PN 60 mg/kg) groups. PN was pre-administered intragastrically once daily for 3 days and with the last administration at 30 min before the operation in the fourth day. Neurological deficit scores, brain water content and infarct volume were measured at 24h after pMCAO. Western blot and qRT-PCR were employed to determine the expressions of pAkt, Nrf2, HO-1 and claudin-5. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by spectrophotometer. RESULTS: Compared with Vehicle group, PN significantly alleviated neurological deficit, infarct volume and brain edema (P<0.05), upregulated the expression of pAkt, Nrf2, HO-1 and SOD (P<0.05), decreased the level of MDA (P<0.05). Meanwhile, the expression of claudin-5 was also enhanced. CONCLUSIONS: PN reduced ischemic brain injury after pMCAO; this effect may be accompanied with upregulation of pAkt, Nrf2, HO-1 and ameliorating BBB permeability.

Bicyclol upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia.

UNLABELLED: Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated. METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer. RESULTS: Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05). CONCLUSIONS: Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.

Neuroprotective effect of bicyclol in rat ischemic stroke: down-regulates TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulates claudin-5 expression.

BACKGROUND: Inflammatory damage aggravates the cerebral ischemic pathological process and may pave a new way for treatment. Bicyclol has been proved to elicit a series of biologic effects through its anti-inflammatory property in treating hepatitis and hepatic ischemic/reperfusion injury. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of bicyclol and the underlying mechanisms. METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: permanent middle cerebral artery occlusion (pMCAO), Vehicle (pMCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50 mg/kg), By-H (Vehicle+bicyclol 100 mg/kg) and Sham operated group. Bicyclol was administered intragastrically once a day for 3 days, after 1h of bicyclol pretreatment on the third day; rat brain ischemia was induced by pMCAO. Neurological deficit, infarct volume, and brain edema were measured at 24 h after stroke. Immunohistochemistry, Western blot and real-time quantitative PCR were used to detect the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9, claudin-5. RESULTS: Compared with pMCAO group, bicyclol significantly ameliorated neurological deficit, decreased infarct volume and edema, and down-regulated the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9 (P<0.05). Meanwhile, the expression of claudin-5 was increased (P<0.05). CONCLUSIONS: Bicyclol has neuroprotective effect on cerebral ischemia, and this protection may be through down-regulating TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulating claudin-5 expression.