Résumé
Objective:To investigate the evaluation value of one-stop whole-brain dynamic volume CT angiography and CT perfusion imaging (CTA-CTP) in the cynomolgus monkeys models of middle cerebral artery occlusion (MCAO).Methods:Ten adult cynomolgus monkeys were selected and examined by head and neck CTA-CTP and craniocerebral MRI to rule out craniocerebral space-occupying lesions or cerebrovascular malformation. Under guidance of digital substraction angiography (DSA), the right femoral artery was dissected and monkey autologous thrombosis was injected into the right middle cerebral artery (MCA) through microcatheter to prepare MCAO models. Whole brain DSA was performed intraoperatively to observe whether the model was successfully prepared, and head and neck CTA-CTP was performed 24 h and 7 d after modeling to determine the locations and brain blood flow changes of ischemic lesions. The monkeys were sacrificed 8 d after modeling, and the brain tissues were stained with 2,3,5-triphenyltetrazolium chloride (TTC).Results:Among the 10 cynomolgus monkeys, one was excluded because of preoperative cerebrovascular malformation, and one died of cerebral hernia caused by cerebral hemorrhage during the experiment. The remaining 8 MCAO models were successfully prepared. Intraoperative DSA orthography showed unclear M1 segment and distal branch of MCA. Brain CT scan 24 h and 7 d after modeling showed obvious cerebral ischemic lesions in the right MCA blood supply area, and the infarct extent 7 d after surgery was more obvious than that 24 h after surgery. CTA examination showed obvious blood flow interruption imaging in the in M1 segment of MCA on the right side, the distal vessels were not clearly displayed and the distal branches of the infarct side 7 d after surgery were obvious decreased as compared with those 24 h after surgery. CTP scan showed that the cerebral blood volume of the right cerebrum was obviously reduced as compared with that of the left cerebrum, which was consistent with the blood supply area of MCA; and the infarct cores and penumbra areas 7 d after surgery were obvious increased as compared with those 24 h after surgery. TTC staining showed that the ischemic lesions of the brain tissue on the slices were gray and involved multiple layers, and the range was roughly consistent with the infarction sites shown by DSA and CT imaging.Conclusion:One-stop whole brain dynamic volume CTA-CTP has good evaluation value in imaging findings in MCAO animal models.
Résumé
BACKGROUND:Buyanghuanwu decoction has excel ent neuroprotective effect and can efficiently suppress nerve cel apoptosis caused by cerebral ischemia-reperfusion injury. OBJECTIVE:To investigate the effect and mechanisms of Buyanghuanwu decoction on neuronal apoptosis around hematoma in cerebral hemorrhage rats. METHODS:Seventy-two adult Sprague-Dawley rats were randomly divided into sham operation group, model group, Buyanghuanwu decoction group, and Ginkgo biloba group. Except the sham operation group, rat models of cerebral hemorrhage were established in other three groups. At 2 days after modeling, rats in the Buyanghuanwu group and Ginkgo biloba group were given Buyanghuanwu decoction 26 g/(kg?d)and Ginkgo biloba 3.5 mg/(kg?d) daily by gavage, for 14 consecutive days. Rats in the sham operation group and model group received an equal volume of saline for 14 consecutive days. After the last administration, brain tissue was obtained. TUNEL assay was utilized to detect neuronal apoptosis. Immunohistochemistry was used to detect PI3K, Akt, Bcl-2, and BAX protein expression. Wet and dry weight method was used to detect brain water content. Evans Blue assay was utilized to determine blood-brain barrier permeability. RESULTS AND CONCLUSION:(1) Compared with the sham operation group, the number of apoptotic neurons, brain water content, Evans blue content and PI3K, Akt, Bcl-2, BAX protein expression increased in the model group (P<0.05). (2) Compared with the model group, the number of apoptotic neurons, BAX protein expression, brain water content and Evans blue content were significantly reduced in the Buyanghuanwu group and Ginkgo biloba group (P<0.05), but PI3K, Akt and Bcl-2 protein expression was significantly increased (P<0.05). (3) Results suggested that Buyanghuanwu decoction inhibited neuronal apoptosis and protected brain tissue by reducing blood-brain barrier permeability, cerebral edema, and by activating PI3K/Akt signaling pathway, regulating Bcl-2 and BAX protein expression ratio.
Résumé
BACKGROUND:Buyang HuanwuDecoction is commonly used in clinical medicine in treatment of intracerebral hemorrhage. Previous studies have been found that it has excelent neuroprotective effect, can efficiently inhibit the apoptosis of nervecels. Autophagic activity is closely related to apoptosis of nerve cels. CXCR4-PI3K autophagy signaling pathway has been verified in clinic. However, the effect of Buyang HuanwuDecoction is poorly understood. There is no study on Beclin-1 in the neuroprotective studies ofBuyang HuanwuDecoction. OBJECTIVE:To explore the effects ofBuyang HuanwuDecoction on CXCR4-PI3K autophagy signaling pathway and Beclin-1 in rats with cerebral hemorrhage and related mechanisms. METHODS:According to Rosenberg method, a rat model of cerebral hemorrhage was replicated and intragastricaly administeredBuyang HuanwuDecoction. Western blot assay was used to measure Beclin-1 protein. Immunohistochemical method was utilized to detect the expression of PI3K, AKT, stromal cel derived factor 1 and CXCR-4 protein. TUNEL assay was applied to identify apoptosis. RESULTS AND CONCLUSION:(1) After administration,Buyang HuanwuDecoction could reduce the number of neuronal apoptosis in rats with intracerebral hemorrhage, up-regulate the expression of Beclin-1, PI3K, AKT, stromal cel derived factor 1, and CXCR-4 protein, and exert neuroprotective effect. (2)Buyang HuanwuDecoction could activate CXCR4-PI3K autophagy signal transduction pathway, both to stimulate autophagy and to regulate autophagy state, can inhibit apoptosis, and exert cerebral protective effect.