Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats / 中国结合医学杂志

OBJECTIVE@#To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats.@*METHODS@#The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored.@*RESULTS@#Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01).@*CONCLUSIONS@#Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage / 中国结合医学杂志

OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

Baicalin Reduces Early Brain Injury after Subarachnoid Hemorrhage in Rats / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of baicalin on subarachnoid hemorrhage (SAH) in rats and explore the potential mechanisms.@*METHODS@#Sprague-Dawley rats underwent experimental SAH and received treatment with baicalin at 10 or 50 mg/kg after 2 and 12 h of SAH. Neurological scores, brain water content, Evans-blue extravasation, and levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), matrix metalloproteinase-9 (MMP-9), aquaporin 4 (AQP4), occludin, and zonulaoccludens-1 (ZO-1) were detected in the brain by Western blot. Heme oxygenase-1 (HO-1) was detected by quantitative polymerase chain reaction, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by enzyme-linked immunosorbent assay.@*RESULTS@#Baicalin attenuated EBI 24 h after SAH in rats (P<0.05). Baicalin elevated neurological scores, GSH-Px, SOD, and increased the expression of Nrf2, NQO1, HO-1, occludin, and ZO-1 in SAH rats (P<0.05 or P<0.01). Baicalin reduced MPO, MDA, and the expression of MMP-9, AQP4, TNF-α, and IL-1β (P<0.05 or P<0.01).@*CONCLUSION@#Baicalin reduced SAH-induced EBI, partially via activation of the Nrf2/HO-1 pathway and inhibition of MMP-9 and AQP4.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice / 中华医学杂志(英文版)

<p><b>Background</b>Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.</p><p><b>Methods</b>We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.</p><p><b>Results</b>We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.</p><p><b>Conclusion</b>The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.</p>

Multimodal endovascular treatment for traumatic carotid-cavernous fistula / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To present our experience in treating traumatic carotid-cavernous fistula (TCCF) by multimodal endovascular treatment.</p><p><b>METHODS</b>The management of 28 patients with TCCF between January 2004 and October 2012 in our hospital was retrospectively analyzed. According to imaging charateristics, 24 cases were categorized into Type I, 3 Type II and 1 Type III. Totally 30 endovascular treatments were performed: Type I TCCFs were obliterated via transvenous approach (7/25), or transarterial approach (18/25) including 6 by detachable balloon occlusion, 6 by microcoil embolization, 3 by Hyperglide balloon-assisted coil embolization and 3 by a combination of detachable balloon and coil embolization. Two patients were treated with closure of internal carotid artery (ICA). Type II TCCFs were treated with transvenous embolotherapy (2/3) or carotid artery compression therapy (1/3). The Type III patient underwent detachable balloon embolization.</p><p><b>RESULTS</b>Immediate postoperative angiography showed recovery in 26 cases. One recurrent TCCF was found 2 weeks after detachable balloon embolization, and then re-obliterated by transarterial coils. Reexamination found balloon deflation and fistula recanalization in 1 patient one month after combination of detachable balloons and coil embolization, which was cured by a second treatment via transvenous approach. The immediate angiography revealed residual blood flow in 4 patients. Among them, 2 patients with delayed symptoms at follow-up needed a second treatment, 1 patient recovered after carotid artery compression therapy, and the remaining patient's symptoms disappeared on digital subtraction angiography at five-month follow-up. CT angiography revealed anterior communicating artery aneurysm in the patient who was treated with closure of ICA 4 years later.</p><p><b>CONCLUSION</b>According to results of images, characteristics of the fistula and type of drainage, proper treatment approach and embolic material can maximally heal pathological changes, retain the ipsilateral ICA patency and reduce long-term complications.</p>

Palliative Gamma knife in treating elderly patients with brain metastasis / 中华神经医学杂志

Objective To evaluate the therapeutic effect of Gamma knife radiosurgery (GKRS) on patients aged ≥65 years who presented with brain metastasis. Methods The clinical treatment and follow-up data of 134 patients,admitted to and treated with GKRS in our hospital from March 2004 to March 2010,were analyzed.These 134 patients totally underwent 212 GKRS for 403 metastases.The median maximal and marginal doses were (29.3±8.4) Gy and (15.9±4.8) Gy,respectively.Kaplan-Meier survivor analysis was utilized to calculate the median survive time and multivariate analysis was employed to determine the clinical factors influencing the treatment outcome. Results Of the 372 metastasis followed by imaging,complete response was achieved in 66 lesions (17.7％),partial response in 174 lesions (46.8％),no change in 94 lesions (25.3％),and partial progression in 38 lesions (10.2％).Median survival was 10.9 months.Grade of recursive partitioning analysis (RPA),number of tumors,scores of Karnofsky performance scale (KPS) and status of primary malignancies were found to be factors influencing the efficacy (P＜0.05). Conclusion GKRS for patients aged over 65 years with brain metastases is an effective and safe treatment method that appears to improve survival and is helpful in maintaining relative good life quality in selected population

Posttraumatic hydrocephalus associated with decompressive cranial defect in severe brain-injured patients / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the occurrence of posttraumatic hydrocephalus (PTH) in severe brain- injured patients who underwent decompressive craniectomy (DC) and to discuss the management.</p><p><b>METHODS</b>A total of 389 patients suffering from severe head trauma between January 2004 and May 2010 were enrolled in this study. Clinical data were analyzed retrospectively. Of them, 149 patients who underwent DC were divided into two groups according to the presence of PTH: hydrocephalus group and nonhydrocephalus group. Clinical factors including preoperative Glasgow Coma Score (GCS), bilateral or unilateral decompression, and duraplasty in DC were assessed by single factor analysis to determine its relationship with the occurrence of PTH.</p><p><b>RESULTS</b>Of the 149 patients undergoing DC, 25 (16.8%) developed PTH; while 23 developed PTH (9.6%) among the rest 240 patients without DC. Preoperative GCS, bilateral or unilateral decompression, duraplasty in DC were significantly associated with the development of PTH. Ventriculoperitoneal shunt was performed on 23 of 25 patients with PTH after DC. Frontal horn was preferred for the placement of the catheter. Sixteen of them were operated upon via frontal approach and 7 via occipital approach. After shunt surgery, both radiological and clinical improvements were confirmed in 19 patients. Radiological improvement was found in 2 patients. One patient died eventually of severe pneumonia. Shunt-related infection occurred in 1 patient, which led to the removal of the catheter.</p><p><b>CONCLUSIONS</b>It is demonstrated that the occurrence of PTH is high in patients with large decompressive skull defect. Patients with low GCS and bilateral decompression tend to develop PTH after DC. Duraplasty in DC might facilitate reducing the occurrence of PTH. Patients with PTH concomitant skull defect should be managed deliberately to restore the anatomical and physiological integrity so as to facilitate the neurological resuscitation.</p>

Chronic subdural hematoma associated with sylvian arachnoid cyst in juvenile athletes: report of two cases and literature review / 中华创伤杂志(英文版)

The association of chronic subdural hematoma (CSDH) and arachnoid cyst (AC) is uncommon. We reported 2 juvenile athletes with CSDH associated with AC which occurred in their daily sports activities and reviewed the literature. Both of them were treated surgically, with satisfactory outcome. AC is a common predisposing factor in young patients with CSDH. The complication of intracranial bleeding is an indication for surgical management. Though there are still controversies in the treatment of asymptomatic AC, it is the consensus that the patients with AC should avoid violent sports so as to reduce the incidence of intracranial hemorrhage resulted from head injuries.

Changes of cortical somatosensory evoked potentials under different levels of ischemia in the spinal cord / 中华神经医学杂志

Objective To provide the theoretical basis for the application of cortical somatosensory evoked potential (CSEP) in monitoring the function of the spinal cord to prevent postoperative neurological dysfunction. Methods Thirty-three New Zealand rabbits were randomly divided into 6 groups: 8 were chosen as control group to eliminate the influence of anesthesia and surgery on the evoked potential; the other 25 were assigned to 5 sub-experimental groups (n=5) according to the artery number being ligatured in the left renal arteries and the spinal arteries. Baseline evoked potential in each group was noted immediately after anesthesia; the CSEP were recorded at different time points (before vascular ligation, 30 min and 2 d after vascular ligation). Motor functions were assessed after narcotic conscious and 2 d after vascular ligation. The specimens were taken for HE staining. Results The latency was not sensitive to spinal cord ischemia and no significant difference of that was found between the experimental groups and the control group (P>0.05); except that, the changes of theamplitudes were very complex and the specificity of motor function was decreased. The amplitude reduced and then gradually restored in the 2, 3 and 4 levels of ligation. The changes of amplitude could indicate the degree of pathological damage in the spinal cord and its motor function. Conclusion Complex amplitude of somatosensory evoked potential can be found in the acute phase of ischemia in the spinal cord. Specificity of motor function is poor resulting from its signal averaging process. Motor evoked potential monitoring in the operation should also be added in the detection of the spinal cord.

Tissue transglutaminase protein expression in human brain tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate expression of tissue transglutaminase (tTG) protein and its role in carcinogenesis of brain tumors.</p><p><b>METHODS</b>tTG protein was detected by immunohistochemical method in 62 astrocytomas, 18 oligodendrogliomas, 30 benign meningiomas, 30 pituitary adenomas and 10 normal brain tissues.</p><p><b>RESULTS</b>(1) In brain tumors, tTG protein expression was heterogeneous locating in tumor and endothelial cells. (2) Immunoreactivity of tTG protein was significantly different between different grades of astrocytomas. (3) Expression intensity of tTG protein in glioma was higher than that in benign brain tumors. (4) Strong expression of tTG protein in tumor cell was obtained around the necrosis foci and apoptotic cells in astrocytomas.</p><p><b>CONCLUSIONS</b>tTG protein expression contributed to tumor malignant progression in malignant brain tumors.</p>