A simple, organized web-based system improved the transfer efficiency and patient outcomes for endovascular thrombectomy in regional stroke network.

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

Minimally Invasive Resection of a Foraminal Lumbar Root Schwannoma.

Background and Importance: This video article reports a rare case of a right L5/S1 foraminal root schwannoma that presents the natural course of the disease, imaging findings, treatment protocol, operative procedure, and highlights some of the possible surgical complications. Clinical Presentation: Magnetic resonance imaging (MRI) revealed an intradural, extramedullary, well-enhanced mass at the right L5/S1 level. The operative procedure involved a right minimal L5/S1 laminotomy/foraminotomy posteriorly to open the right L5 root. The facet joints were preserved to prevent spinal instability. The tumor was located along the root after opening the right L5/S1 foramen. Intraoperative electromyography (IOM) was conducted to detect any nerve injury in the patient. After opening the dura, the tumor was carefully separated from the normal root nerve under IOM monitoring. The mass was removed piece-by-piece using mini-forceps. Conclusion: Histopathological examination confirmed the diagnosis of a schwannoma. The patient recovered without incident after surgery with minimal soreness and numbness in the right leg.

Clinical Outcome and Safety of Lumboperitoneal Shunt in the Treatment of Non-Obstructive Hydrocephalus.

Objective: This study aimed to evaluate the functional outcomes of lumboperitoneal (LP) shunt for the treatment of non-obstructive hydrocephalus. Methods: We retrospectively studied the clinical surgical results of 172 adult patients with hydrocephalus who underwent LP shunt surgery between June 2014 and June 2019. Data regarding the following were collected: pre- and postoperative symptom status, third ventricle width changes, Evans index, and postoperative complications. Additionally, the baseline and follow-up Glasgow Coma Scale (GCS) score, Glasgow Outcome Scale (GOS), and Modified Rankin Scale (mRS) scores were investigated. All patients were followed up for ≥12 months using clinical interview and braining imaging using computed tomography (CT) scan or magnetic resonance imaging (MRI). Results: Majority of patients presented with normal pressure hydrocephalus as the etiology of their disease (48.8%), followed by cardiovascular accident (28.5%), trauma (19.7%), and brain tumor (3%). The mean GCS, GOS, and mRS improved postoperatively. The average period from symptomatic onset to surgery was 402 days. The average width of the third ventricle on CT scan or MRI was 11.43 mm preoperatively and 10.8 mm postoperatively (P<0.001). The Evans index improved from 0.258 to 0.222 after operation. The symptomatic improvement score was 7.0, with a complication rate of 7%. Conclusion: Significant improvement was observed in the functional score and brain image after LP shunt placement. Moreover, the satisfaction with symptomatic improvement after surgery remains high. LP shunt operation is a viable alternative in the treatment of non-obstructive hydrocephalus due to the low complication rate, fast recovery, and high satisfaction.

Short-term lithium treatment protects the brain against ischemia-reperfusion injury by enhancing the neuroplasticity of cortical neurons.

OBJECTIVES: Lithium exerts a broad neuroprotective effect on the brain. This study examined whether lithium exerts therapeutic effects on stroke by restoring neural connections at the ischemic core of cortices post brain insult. METHODS: We treated rats with lithium or vehicle (saline) every 24 h for the first 72 h, starting at the beginning of reperfusion after inducing middle cerebral artery occlusion (MCAO) in rats. Somatosensory evoked potential (SSEP) recording and behavioral testing were employed to evaluate the beneficial effects of lithium treatment. To examine the effects of lithium-induced neuroplasticity, we evaluated the dendritic morphology in cortex pyramidal cells and the primary neuronal cell culture that underwent brain insults and oxygen and glucose deprivation (OGD), respectively. RESULTS: The results demonstrated that rats subjected to MCAO had prolonged N1 latency and a decreased N1/P1 amplitude at the ipsilateral cortex. Four doses of lithium reduced the brain infarction volume and enhanced the SSEP amplitude. The results of neurobehavioral tests demonstrated that lithium treatment improved sensory function, as demonstrated by improved 28-point clinical scale scores. In vitro study results showed that lithium treatment increased the dendritic lengths and branches of cultured neurons and reversed the suppressive effects of OGD. The in vivo study results indicated that lithium treatment increased cortical spine density in various layers and resulted in the development of the dendritic structure in the contralateral hemisphere. CONCLUSION: Our study confirmed that neuroplasticity in cortical neurons is crucial for lithium-induced brain function 50 recovery after brain ischemia.

Cinnamophilin enhances temozolomide-induced cytotoxicity against malignant glioma: the roles of ROS and cell cycle arrest.

BACKGROUND: Temozolomide (TMZ) has been widely used to treat glioblastoma multiforme (GBM). However, many mechanisms are known to quickly adapt GBM cells to chemotherapy with TMZ, leading to drug resistance and expansion of tumor cell populations. METHODS: We subjected human glioblastoma cell lines and an animal model of glioblastoma xenografts with TMZ-based adjuvant treatments to evaluate the synergistic effect of cinnamophilin (CINN), a free radical scavenger. RESULTS: Our results showed that the combined treatment of CINN and TMZ potentiated the anticancer effect and apoptotic cell death in glioma cell lines and enhanced antitumor action in glioma xenografts. TMZ induced reactive oxygen species (ROS) burst and elevated G2 arrest in glioma cells. The CINN-suppressed ROS burst in TMZ-treated glioma cells might be associated with increased apoptosis, as indicated by the upregulation of TUNEL-positive glioma cells. CINN-pretreated glioma cells exhibited increased cyclin B expression and reduced phosphorylation of Cdk1, suggesting reduced G2 arrest in the combined treatment group. Moreover, CINN lowered the protein level of LC3, a hallmark of autophagy, in TMZ-treated cells. CONCLUSIONS: These findings suggest that CINN may restore TMZ toxicity in glioma cancer by suppressing the ROS/G2 arrest pathway.

Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKR­like endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.

Magnolol protects against ischemic-reperfusion brain damage following oxygen-glucose deprivation and transient focal cerebral ischemia.

In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin­6, tumor necrosis factor­a and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygen­glucose deprivation­induced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult. In a rat model of stable ischemia, compared with a vehicle­treated ischemic control, pretreatment with magnolol (0.01­1 mg/kg, intravenously) significantly reduced brain infarction following ischemic stroke, and post­treatment with magnolol (1 mg/kg) remained effective and significantly reduced infarction when administered 2 h following the onset of ischemia. Additionally, magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide anions at the border zones of infarction and reduced oxidative damage in the ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the immunoreactions of 8­hydroxy­2'­deoxyguanosine and 4­hydroxynonenal. Thus, magnolol was revealed to protect against ischemia­reperfusion brain damage. This may be partly attributed to its antioxidant, radical scavenging and anti­inflammatory effects.

Application of flow cytometry for evaluating clinical prognosis and histopathological grade of human glioma.

OBJECTIVES: Flow cytometry was applied to predict the biological parameters of tumor behavior based on the DNA content distribution of tumors. We used flow cytometry to determine the number of cell cycles for the characterization of intracranial gliomas and its possible prognostic role. METHODS: Flow cytometric analysis of the DNA content was performed for 37 fresh operative glioma specimens. The expression of Ki-67 in glioma specimens was detected using immunohistochemistry staining. The check points of G2/M-phase fractions, cyclin B, and pCdk1 (Y15) were analyzed using Western immunoblotting. RESULTS: Compared to low-grade (grade I/II) gliomas, significant differences in the Ki-67, cyclin B, G2/M-phase, and S+G2/M-phase expressions were found in high-grade (grade III/IV) gliomas. Furthermore, receiver operating characteristic (ROC) analysis indicated optimal cutoff points for the G2/M-phase and S+G2/M-phase fractions of 13.47 and 17.26%, respectively, which can be used to differentiate cases with low- and high-grade gliomas. Additionally, both G2/M-phase and S+G2/M-phase fractions had significant association with the expression of Ki-67 in the gliomas. The gliomas were classified by the DNA content. We found that patients with high-grade glioma had worse survival rate than patients with low-grade glioma. Meanwhile, ROC curve analysis gave cutoffs for G2/M-phase of 9.4% and for S+G2/M-phase fractions of 15.04% as best predicting survival. The patients with glioma had poor survival when the levels of G2/M-phase and S+G2/M-phase were more than 9.4 and 15.04%, respectively. In contrast, no significant association between the DNA content of glioma patients and their age, tumor recurrence, and tumor size was found. DISCUSSION: Our results indicate that flow cytometry analysis for G2/M-phase and S+G2/M-phase fractions can be used for tumor grading for rapidly differentiating low- from high-grade gliomas.

The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.

BACKGROUND: Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas. METHODS: The specimens were obtained from fresh tumoral tissues of 43 microsurgically resected meningiomas as approved by the institutional review board. The presence of G2/M-phase and S+G2/M-phase fractions were analyzed and correlated with the proliferation index of Ki-67 and the World Health Organization grading. The check point of G2/M-phase fraction, cyclin B, and pCdk1 (Y15), were analyzed by Western blotting. RESULTS: Our results showed that there were significant differences in Ki-67, G2/M-phase, S+G2/M-phase fractions, and cyclin B between benign and atypical/anaplastic meningiomas. The optimal cutoff point of G2/M-phase and S+G2/M-phase fractions were 5.12 and 7.52%, respectively, and this can be used to discriminate those cases with benign or atypical/anaplastic meningiomas. Besides, both the G2/M-phase and S+G2/M-phase fractions were correlated well with Ki-67 and the histopathological features such as focal necrosis, infiltration of dura mater and mitotic activity. In addition, the occurrence of tumor recurrence and patient age were correlated to the G2/M-phase and S+G2/M-phase fractions, respectively. The G2/M-phase and S+G2/M-phase fractions, however, did not correlate well with histologic invasion to adjacent bone, sinus, or brain tissues. CONCLUSIONS: The use of flow cytometry facilitates additional information for G2/M-phase and S+G2/M-phase fractions represent tumoral grading and risk of recurrence in patients with meningiomas.

High-grade glioma in a patient with breast cancer.

Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s) were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.

Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period.

Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD-95, GAP-43, and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7 days postinsult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days postinsult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly upregulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P<0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement in GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P<0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days postinsult (P<0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95, and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity and to enhance long-term neuroprotection, neuroplasticity, and brain remodeling in stroke rats.

Melatonin inhibits matrix metalloproteinase-9 (MMP-9) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells and a mouse model of meningitis.

We explored anti-inflammatory potential of melatonin against the lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. RAW 264.7 and BV2 cells were stimulated by LPS, followed by the treatment with melatonin or vehicle at various time intervals. In a mouse model of meningitis induced by LPS, melatonin (5mg/kg) or vehicle was intravenously injected at 30min postinsult. The activity of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was determined by gelatin zymography. Nuclear factor-kappa B (NFκB) translocation and binding activity were determined by immunocytochemistry and electrophoretic mobility shift assay (EMSA). Our results showed that either pretreatment or cotreatment with melatonin at 50-500 µm effectively inhibited the LPS-induced proMMP-9 activation in the RAW 264.7 and BV2 cells, respectively (P<0.05). This melatonin-induced proMMP-9 inhibition remained effective when treatment was delayed up to 2 and 6hr postinsult for RAW 264.7 and BV2 cells, respectively (P<0.05 for both groups). Additionally, melatonin significantly attenuated the rises of circulatory and cerebral MMP-9 activity, respectively (P<0.05) and reduced the loss of body weight (P<0.05) in mice with meningitis. Moreover, melatonin (50µm) effectively inhibited nuclear factor-kappa B (NFκB) translocation and binding activity in the LPS-treated RAW 264.7 and BV2 cells, respectively (P<0.05). These results demonstrate direct inhibitory actions of melatonin against postinflammatory NFκB translocation and MMP-9 activation and highlight its ability to inhibit systemic and cerebral MMP-9 activation following brain inflammation.