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OBJECTIVEIntraventricular hemorrhage (IVH) is found in approximately 40% of intracerebral hemorrhages and is associated with increased mortality and poor functional outcome. Cognitive impairment is one of the complications and occurs due to various pathological changes. Amyloid beta (Aβ) accumulation and neuroinflammation, and the Alzheimer disease–like pathology, may contribute to cognitive impairment. Iron, the degradation product of hemoglobin, correlates with Aβ. In this study, the authors investigated the correlation between Aβ accumulation with enhanced neuroinflammation and cognitive impairment in a rat model of IVH.METHODSNine male Sprague-Dawley rats underwent an intraventricular injection of autologous blood. Another 9 rats served as controls. Cognitive function was assessed by the Morris water maze and T-maze rewarded alternation tests. Biomarkers of Aβ accumulation, neuroinflammation, and c-Jun N-terminal kinase (JNK) activation were examined.RESULTSCognitive function was impaired in the autologous blood injection group compared with the control group. In the blood injection group, Aβ accumulation was observed, with a co-located correlation between iron storage protein ferritin and Aβ. Beta-site amyloid precursor protein cleaving enzyme–1 (BACE1) activity was elevated. Microgliosis and astrogliosis were observed in hippocampal CA1, CA2, CA3, and dentate gyrus areas, with elevated proinflammatory cytokines tumor necrosis factor–α and interleukin-1. Protein levels of phosphorylated JNK were increased after blood injection.CONCLUSIONSAβ accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.

Phase-amplitude coupling (PAC) between the phase of low-frequency oscillations and the power of high-frequency activity plays a functional role in neuronal computation and information transfer. Traditional Hilbert transform-based PAC methods assume that neuronal activity is narrowband, sinusoidal, and sustained. However, natural neuronal signals often violate these three assumptions, creating a potential confound for the interpretation of PAC results. In this study, we present a new method, called Tau-Modulation, that does not require these assumptions to be met. We use this method to identify task-relevant neuronal networks in human electrocorticographic signals. Our results show that Tau-Modulation can identify these networks and characterize the strength and frequency of wideband low-frequency coupling with broadband gamma activity. Thus, Tau-Modulation might provide for a robust approach to analyzing neuronal signals and pave the way for new insights on brain functions.

Stereo-electroencephalography (SEEG) is an intracranial recording technique in which depth electrodes are inserted in the brain as part of presurgical assessments for invasive brain surgery. SEEG recordings can tap into neural signals across the entire brain and thereby sample both cortical and subcortical sites. However, even though signal referencing is important for proper assessment of SEEG signals, no previous study has comprehensively evaluated the optimal referencing method for SEEG. In our study, we recorded SEEG data from 15 human subjects during a motor task, referencing them against the average of two white matter contacts (monopolar reference). We then subjected these signals to 5 different re-referencing approaches: common average reference (CAR), gray-white matter reference (GWR), electrode shaft reference (ESR), bipolar reference, and Laplacian reference. The results from three different signal quality metrics suggest the use of the Laplacian re-reference for study of local population-level activity and low-frequency oscillatory activity.

Objective The precise localization of intracranial electrodes is a fundamental step relevant to the analysis of intracranial electroencephalography (iEEG) recordings in various fields. With the increasing development of iEEG studies in human neuroscience, higher requirements have been posed on the localization process, resulting in urgent demand for more integrated, easy-operation and versatile tools for electrode localization and visualization. With the aim of addressing this need, we develop an easy-to-use and multifunction toolbox called iEEGview, which can be used for the localization and visualization of human intracranial electrodes. Approach iEEGview is written in Matlab scripts and implemented with a GUI. From the GUI, by taking only pre-implant MRI and post-implant CT images as input, users can directly run the full localization pipeline including brain segmentation, image co-registration, electrode reconstruction, anatomical information identification, activation map generation and electrode projection from native brain space into common brain space for group analysis. Additionally, iEEGview implements methods for brain shift correction, visual location inspection on MRI slices and computation of certainty index in anatomical label assignment. Main results All the introduced functions of iEEGview work reliably and successfully, and are tested by images from 28 human subjects implanted with depth and/or subdural electrodes. Significance iEEGview is the first public Matlab GUI-based software for intracranial electrode localization and visualization that holds integrated capabilities together within one pipeline. iEEGview promotes convenience and efficiency for the localization process, provides rich localization information for further analysis and offers solutions for addressing raised technical challenges. Therefore, it can serve as a useful tool in facilitating iEEG studies.

Brain arteriovenous malformations (AVMs) which associate with angiogenesis due to local hypertension, chronic cerebral ischaemia and tissue hypoxia usually lead to haemorrhage, however, the therapeutic medicine for the disease is still lacking. 2‐methoxyestradiol (2‐ME) has been shown effective in the anti‐angiogenic treatment. This study was conducted to examine whether and how 2‐ME could improve the vascular malformations. Intracranial venous hypertension (VH) model produced in adult male Sprague‐Dawley rats and culture of human umbilical vein endothelial cells (HUVECs) at the anoxia condition were used to induce in vivo and in vitro angiogenesis, respectively. Lentiviral vectors of ID‐1 and p53 genes and of their siRNA were intracranially injected into rats and transfected into HUVECs to overexpress and down‐regulate these molecules. 2‐ME treatment not only reduced the in vivo progression of brain tissue angiogenesis in the intracranial VH rats and the in vitro increases in microvasculature formation, cellular migration and HIF‐1α expression induced by anoxia in HUVECs but also reversed the up‐regulation of ID‐1 and down‐regulation of p53 in both the in vivo and in vitro angiogenesis models. All of the anti‐angiogenesis effects of 2‐ME observed in VH rats and anoxic HUVECs were abrogated by ID‐1 overexpression and p53 knockdown. Our data collectively suggest that 2‐ME treatment inhibits hypoxia/anoxia‐induced angiogenesis dependently on ID‐1 down‐regulation and p53 up‐regulation, providing a potential alternative medical treatment for un‐ruptured AVM patients.

BACKGROUND The molecular mechanism of brain arteriovenous malformation (BAVM) is largely unknown. Intracranial venous hypertension (VH) may enhance focal angiogenesis and promote BAVM development and progression. A rat VH model effectively simulates the hemodynamic microenvironment of this disease. OBJECTIVE To explore the effect of doxycycline in VH-related angiogenesis, as well as the role of matrix metalloproteinase-3 (MMP-3) and other molecular factors. METHODS A rat VH model was generated by common carotid artery and distal external jugular vein anastomosis. Microvessel density (MVD) in the perisinus area and expression of MMP-3/2/9, VEGF, TIMP-1, TGF-β, and HIF-1α were examined, with and without daily doxycycline treatment for 4 wk. The effects of doxycycline were verified in Vitro using human brain microvascular endothelial cells (HBMECs). MMP-3 overexpression or knockdown in HBMECs was used to confirm the role of MMP-3 in cell functions. RESULTS MVD in the perisinus cortex was greatly increased after VH. Doxycycline decreased MVD, suppressed MMP-3 overexpression, and reduced VEGF, TGF-β, and TIMP-1 levels compared with the controls (P < .05). In Vitro, doxycycline decreased HBMEC migration, tube formation, and the mRNA, protein, and enzymatic activity levels of MMP-3. MMP-3 overexpression in HBMECs promoted migration, while knockdown of MMP-3 significantly attenuated proliferation, migration, and tube formation (P < .05). CONCLUSION Our findings indicate that MMP-3 plays an important role in VH-related angiogenesis and the promotion of vascular remodeling. Suppression of MMP-3 overexpression by doxycycline may provide a potential strategy for inhibiting BAVM development.

In this work, electrocorticographic temporal alteration mapping (ETAM) was proposed for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs) within [0.05 3] Hz low frequency band. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM), which was based on high frequency spectrum dynamics. Five patients (2 epilepsy cases and 3 tumor cases) were enrolled in this study. Each patient had intraoperative direct electrocortical stimulation (DECS) procedure for motor cortex localization, and the patient was required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results shown that the proposed ETAM method had a high performance in sensitivity (81.82%) and specificity (94.33%) for identifying sites which exhibited positive DECS motor responses. No significant difference in sensitivity was observed between ETAM and EFAM methods. However, the proposed ETAM was much higher in specificity as compared with EFAM (94.33% vs. 86.08%). Our results indicated that for the intraoperative functional brain mapping, ETAM was a promising novel approach for motor cortex localization and had a great potential to reduce the needs for cortical electrical stimulation.

Objective To evaluate the efficacy of surgery as a treatment for supratentorial cerebral cavernous malformation–associated epilepsy (SCCMAE) and determine the factors that influence outcomes. Methods During the 5-year period from 2005 to 2009, this study included 181 consecutive patients who were diagnosed with SCCMAE and surgically treated in a single institution. Each patient was followed up for at least 5 years postoperatively. A time-to-event analysis was performed using Kaplan-Meier curves and Cox regression models to evaluate the associated risk factors. Results The age at seizure onset was 30.6 ± 14.3 years, and the age at the time of surgery was 33.4 ± 14.6 years. The female/male ratio was 0.81:1. The mean diameter of the cerebral cavernous malformations (CCMs) was 2.0 cm. For CCMs involving eloquent brain areas, the CCM was removed with (in 14 cases) or without (in 28 lesions) the peripheral hemosiderin. None of the patients had long-term neurologic disabilities. An Engel class I outcome was achieved in 89.0%, 83.4%, 81.8%, and 80.1% of the patients after 6 months, 1 year, 2.5 years, and 5-years of follow-up, respectively. In patients who were class I after 1 year, the prevalence of seizure remission 5 years postoperatively was 96.0% (95% confidence interval, 94.4%–97.6%). Conclusions This study supports the efficacy of using surgery to treat SCCMAE. A shorter duration of preoperative epilepsy was associated with better seizure control after surgery, and patient status at the 1-year follow-up was a reliable indicator of long-term Engel class I epilepsy control.

Stereo-electroencephalographic (SEEG) depth electrodes were used to record neural activity from deep brain structures in this study. By localizing all the electrodes into the individual brain, we found that areas that are inside of central sulcus occurred obvious hand-movement-related modulation when the subjects were performing different hand motion tasks. Then, an asynchronous brain-computer interface which enables the subject to control a prosthetic hand in real time was built. The testing results showed that, using the SEEG signals taken only from five channels, all the participants can not only control the robot prosthesis to be motionless but also can command the device to make three different hand gestures successfully with an average accuracy of 78.70±4.01%.

Iron overload has been regarded as a common cause for refractory epilepsies in patients after hemorrhagic strokes. This study is to examine the potential epilepsy control effect of deferoxamine (DFO), an iron chelator, on a ferric chloride-induced epilepsy rat model. Twenty four rats were divided into 4 groups: group I is blank control group, group II is sham group with intracortical injection of saline, group III is epilepsy group with intracortical injection of iron and saline treatment, group IV is treatment group with intracortical injection of iron and DFO treatment. For the DFO intervention group, a daily dose of 100mg/kg DFO via peritoneal injection was applied for 14days. Outcomes were evaluated by behavioral study, electroencephalography (EEG), magnetic resonance imaging (MRI) scan and tissue analysis. Epilepsies according to behavioral observations and EEG analysis were significantly suppressed after intervention of DFO. Reduction of iron content in the brain cortex was proved by diminished low signal area on T2-MRI images (p=0.006) and tissue analysis (p

OBJECTIVEIntracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats.METHODSThirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and JNK activation were examined.RESULTSIn the Fe-injection group, minocycline suppressed WMI labeled by β-amyloid precursor protein (β-APP) and degraded myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were increased after Fe injection, and could be suppressed by minocycline treatment. In the autologous blood–injection group, β-APP and dMBP/MBP levels increased in the ipsilateral site compared with the contralateral site, which could be suppressed by 7 days of minocycline intervention.CONCLUSIONSIron plays a critical role in WMI after ICH, which can be suppressed by minocycline through reducing the damage induced by Fe.

Background Intracerebral hemorrhage is the least treatable type of stroke and affects millions of people worldwide. Treatment for ICH varies from medicine to surgery, but the rate of mortality and mobility still remains high. Minocycline is a tetracycline antibiotic increasingly recognized for its neuroprotective potential. In earlier studies, we demonstrated that many secondary injuries caused by ICH could be significantly reduced by injection of minocycline in rat models. The following research investigates the role of minocycline in reducing brain injury. Methods Twenty-four rats were administered 100 μl autologous arterial blood injections into the right basal ganglia, treated with minocycline or vehicle and euthanized on the 1st, 3rd, and 7th day. Immunohistochemistry, TUNEL, and western blot analysis were performed to analyze the effects of minocycline on apoptosis and autophagy. Results After the injection of minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7; Beclin-1, LC3BII/I, caspase-3/8 were all suppressed after treatment. The relationship between Cathepsin D and minocycline remained unknown. Conclusions Our studies suggest the potential medicinal value of minocycline, through both anti-autophagy and anti-apoptosis pathways.