Function and organization in dysgenic cortex

1997 ◽  
Vol 87 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Mark C. Preul ◽  
Richard Leblanc ◽  
Fernando Cendes ◽  
Francois Dubeau ◽  
David Reutens ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Right Hemisphere ◽  
Central Area ◽  
Cortical Dysplasia ◽  
Cortical Reorganization ◽  
Sensory Function ◽  
Neurological Deficits ◽  
Cortical Mapping ◽  
Histological Structure

✓ Cerebral dysgenesis is a subject of interest because of its relationship to cerebral development and dysfunction and to epilepsy. The authors present a detailed study of a 16-year-old boy who underwent surgery for a severe seizure disorder. This patient had dysgenesis of the right hemisphere, which was composed of a giant central frontoparietal nodular gray matter heterotopia with overlying large islands of cortical dysplasia around a displaced central fissure. Exceptional insight into the function, biochemistry, electrophysiology, and histological structure of this lesion was obtained from neurological studies that revealed complementary information: magnetic resonance (MR) imaging, [18]fluoro-2-deoxy-d-glucose positron emission tomography (PET), functional PET scanning, proton MR spectroscopic (1H-MRS) imaging, intraoperative cortical mapping and electrocorticography, in vitro electrophysiology, and immunocytochemistry. These studies demonstrated compensatory cortical reorganization and showed that large areas of heterotopia and cortical dysplasia in the central area may retain normal motor and sensory function despite strikingly altered cytoarchitectonic organization and neuronal metabolism. Such lesions necessitate appropriate functional imaging studies prior to surgery and cortical mapping to avoid creating neurological deficits. Integrated studies, such as PET, 1H-MRS imaging, cortical mapping, immunocytochemistry, and electrophysiology may provide information on the function of developmental disorders of cerebral organization.

AWAKE CRANIOTOMY FOR BRAIN TUMORS NEAR ELOQUENT CORTEX

Neurosurgery ◽  
2009 ◽  
Vol 64 (5) ◽  
pp. 836-846 ◽  
Author(s):  
Stefan S. Kim ◽  
Ian E. McCutcheon ◽  
Dima Suki ◽  
Jeffrey S. Weinberg ◽  
Raymond Sawaya ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Neurological Status ◽  
Extent Of Resection ◽  
Sensory Function ◽  
Neurological Deficits ◽  
Cortical Mapping ◽  
Eloquent Areas ◽  
Eloquent Cortex ◽  
Low Incidence ◽  
Intraoperative Localization

Abstract OBJECTIVE Intraoperative localization of cortical areas for motor and language function has been advocated to minimize postoperative neurological deficits. We report herein the results of a retrospective study of cortical mapping and subsequent clinical outcomes in a large series of patients. METHODS Patients with intracerebral tumors near and/or within eloquent cortices (n = 309) were clinically evaluated before surgery, immediately after, and 1 month and 3 months after surgery. Craniotomy was tailored to encompass tumor plus adjacent areas presumed to contain eloquent cortex. Intraoperative cortical stimulation for language, motor, and/or sensory function was performed in all patients to safely maximize surgical resection. RESULTS A gross total resection (≥95%) was obtained in 64%, and a resection of 85% or more was obtained in 77% of the procedures. Eloquent areas were identified in 65% of cases, and in that group, worsened neurological deficits were observed in 21% of patients, whereas only 9% with negative mapping sustained such deficits (P < 0.01). Intraoperative neurological deficits occurred in 64 patients (21%); of these, 25 (39%) experienced worsened neurological outcome at 1 month, whereas only 27 of 245 patients (11%) without intraoperative changes had such outcomes (P < 0.001). At 1 month, 83% overall showed improved or stable neurological status, whereas 17% had new or worse deficits; however, at 3 months, 7% of patients had a persistent neurological deficit. Extent of resection less than 95% also predicted worsening of neurological status (P < 0.025). CONCLUSION Negative mapping of eloquent areas provides a safe margin for surgical resection with a low incidence of neurological deficits. However, identification of eloquent areas not only failed to eliminate but rather increased the risk of postoperative deficits, likely indicating close proximity of functional cortex to tumor.

Functional imaging of cerebral arteriovenous malformations with a comment on cortical reorganization

1996 ◽  
Vol 1 (3) ◽  
pp. E9 ◽  
Author(s):  
Richard Leblanc ◽  
Ernst Meyer ◽  
Robert Zatorre ◽  
Denise Klein ◽  
Alan Evans
Keyword(s):  
Central Region ◽  
Arteriovenous Malformations ◽  
Three Dimensional ◽  
Central Area ◽  
Cavernous Angioma ◽  
Functional Brain Imaging ◽  
Cortical Reorganization ◽  
Cortical Mapping ◽  
Cerebral Arteriovenous Malformations ◽  
Language Areas

Functional brain imaging is poised to become a standard diagnostic tool. The authors review their experience using functional positron emission tomography (fPET) in patients with cerebral arteriovenous malformations (AVMs). Twelve patients, three males and nine females aged 16 to 30 years, 11 with a cerebral AVM and one with a cavernous angioma, of which five were located in the central area and seven in a speech region, underwent fPET and three-dimensional magnetic resonance imaging. These studies were coregistered in stereotactic space and correlated to Brodmann's areas that were identified from the atlas of Talairach and Tournoux. Vibrotactile and/or motor stimulation of the contralateral hand were used to identify the central region in patients whose AVM resided within, or close to, the motor strip, and language tasks specifically designed to activate visual, auditory, expressive, or semantic language were used in patients whose AVM resided within, or close to, Broca's or Wernicke's areas. Somatosensory and motor activation reliably identified the central region in all cases as validated by identification of Brodmann's areas and by intraoperative cortical mapping, which was performed with the patient under local anesthesia. Similarly, language tasks accurately lateralized major language function to one hemisphere concordantly with neuropsychological assessment, including dichotic listening and intracarotid Amytal tests, and localized language areas appropriately as verified by stereotactic coordinates. Functional cerebral imaging is feasible in patients with structural brain lesions. It is a reliable method to identify the relationship of a cerebral AVM to the central region. The determination of a similar relationship to language areas is dependent on the development and further validation of language-based tasks designed to activate visual, auditory, expressive, and semantic aspects of language specific to particular sites within the anterior and posterior speech regions.

scholarly journals The Effects of Early Prenatal Alcohol Exposure on Epigenome and Embryonic Development

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1095
Author(s):  
Essi Wallén ◽  
Pauliina Auvinen ◽  
Nina Kaminen-Ahola
Keyword(s):  
Developmental Disorders ◽  
Current Knowledge ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Neurological Deficits ◽  
Sensitive Period ◽  
Western World ◽  
Increased Risk ◽  
Prenatal Alcohol

Prenatal alcohol exposure is one of the most significant causes of developmental disability in the Western world. Maternal alcohol consumption during pregnancy leads to an increased risk of neurological deficits and developmental abnormalities in the fetus. Over the past decade, several human and animal studies have demonstrated that alcohol causes alterations in epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs. There is an increasing amount of evidence that early pregnancy is a sensitive period for environmental-induced epigenetic changes. It is a dynamic period of epigenetic reprogramming, cell divisions, and DNA replication and, therefore, a particularly interesting period to study the molecular changes caused by alcohol exposure as well as the etiology of alcohol-induced developmental disorders. This article will review the current knowledge about the in vivo and in vitro effects of alcohol exposure on the epigenome, gene regulation, and the phenotype during the first weeks of pregnancy.

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

scholarly journals Depth Electrode Guided Anterior Insulectomy: 2-Dimensional Operative Video

2021 ◽  
Author(s):  
Mauricio Mandel ◽  
Layton Lamsam ◽  
Pue Farooque ◽  
Dennis Spencer ◽  
Eyiyemisi Damisah
Keyword(s):  
Right Hemisphere ◽  
Preoperative Evaluation ◽  
Epileptiform Activity ◽  
Neurological Deficits ◽  
Depth Electrodes ◽  
Depth Electrode ◽  
Patient Reported ◽  
Frontal Operculum ◽  
History Of ◽  
Electroencephalogram Eeg

Abstract The insula is well established as an epileptogenic area.1 Insular epilepsy surgery demands precise anatomic knowledge2-4 and tailored removal of the epileptic zone with careful neuromonitoring.5 We present an operative video illustrating an intracranial electroencephalogram (EEG) depth electrode guided anterior insulectomy.  We report a 17-yr-old right-handed woman with a 4-yr history of medically refractory epilepsy. The patient reported daily nocturnal ictal vocalization preceded by an indescribable feeling. Preoperative evaluation was suggestive of a right frontal-temporal onset, but the noninvasive results were discordant. She underwent a combined intracranial EEG study with a frontal-parietal grid, with strips and depth electrodes covering the entire right hemisphere. Epileptiform activity was observed in contact 6 of the anterior insula electrode. The patient consented to the procedure and to the publication of her images.  A right anterior insulectomy was performed. First, a portion of the frontal operculum was resected and neuronavigation was used for the initial insula localization. However, due to unreliable neuronavigation (ie, brain shift), the medial and anterior borders of the insular resection were guided by the depth electrode reference. The patient was discharged 3 d after surgery with no neurological deficits and remains seizure free.  We demonstrate that depth electrode guided insular surgery is a safe and precise technique, leading to an optimal outcome.

scholarly journals Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules

Zygote ◽  
2021 ◽  
pp. 1-12
Author(s):  
Zhen Jin ◽  
Hua-Feng Shou ◽  
Jin-Wei Liu ◽  
Shan-Shan Jiang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Spindle Microtubule ◽  
Collapsin Response Mediator Protein ◽  
Microtubule Severing ◽  
Structural Support ◽  
Mediator Protein ◽  
Spindle Microtubules ◽  
Transportation Routes ◽  
Normal Meiosis

Abstract Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

scholarly journals MS-1 Surgical strategy for brain tumor based on molecular and functional connectomics profiles

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Tatsuya Abe
Keyword(s):  
Overall Survival ◽  
Brain Tumor ◽  
Standard Procedure ◽  
Awake Craniotomy ◽  
Surgical Strategy ◽  
Neurological Deficits ◽  
Cortical Mapping ◽  
Photodynamic Diagnosis ◽  
Tumor Surgery ◽  
Brain Tumor Surgery

Abstract It is reported that the development of new perioperative motor deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. The maximum safe resection without any neurological deficits is required to improve overall survival in patients with brain tumor. Surgery is performed with various modalities, such as neuro-monitoring, photodynamic diagnosis, neuro-navigation, awake craniotomy, intraoperative MRI, and so on. Above all, awake craniotomy technique is now the standard procedure to achieve the maximum safe resection in patients with brain tumor. It is well known that before any treatment, gliomas generate globally (and not only focally) altered functional connectomics profiles, with various patterns of neural reorganization allowing different levels of cognitive compensation. Therefore, perioperative cortical mapping and elucidation of functional network, neuroplasticity and reorganization are important for brain tumor surgery. On the other hand, recent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. Then, we aimed to identify these biomarkers in pre-operative and/or intra-operative periods, using liquid biopsy, immunostaining and various PCR methods including rapid genotyping assay. In this presentation, we would like to demonstrate our surgical strategy based on molecular and functional connectomics profiles.

scholarly journals Botanical Control of Citrus Green Mold and Peach Brown Rot on Fruits Assays Using a Persicaria acuminata Phytochemically Characterized Extract

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 425
Author(s):  
Melina G. Di Liberto ◽  
Gisela M. Seimandi ◽  
Laura N. Fernández ◽  
Verónica E. Ruiz ◽  
Laura A. Svetaz ◽  
...  
Keyword(s):  
Ecological Model ◽  
Fungal Infections ◽  
Ex Vivo ◽  
Central Area ◽  
Brown Rot ◽  
Phytopathogenic Fungi ◽  
Perennial Herb ◽  
Huh7 Cells ◽  
Gas Chromatography Mass Spectroscopy

Persicaria acuminata (Polygonaceae) is a perennial herb that grows in the central area of Argentina and it is commonly used by native populations to heal infected wounds and other conditions related to fungal infections. In this article, we explored the in vitro antifungal activity of its ethyl acetate extract against a panel of three fruit phytopathogenic fungi including: Penicillium digitatum, P. italicum, and Monilinia fructicola. The sesquiterpenes isolated from the extract were also evaluated against these strains, demonstrating that the dialdehyde polygodial was the responsible for this activity. In order to encourage the use of the extract rather than the pure compound, we displayed ex vivo assays using fresh oranges and peaches inoculated with P. digitatum and M. fructicola, respectively, and subsequently treated by immersion with an extract solution of 250 and 62.5 µg/mL, respectively. There were no statistically significant differences between the treatments with commercial fungicides and the extract over the control of both fruit rots. The concentration of the active compound present in the extract used on fruit experiments was determined by Gas Chromatography-Mass Spectroscopy. Finally, cytotoxicity evaluation against Huh7 cells showed that P. acuminata extract was less cytotoxic than the commercial fungicides at the assayed concentrations. After these findings we could conclude that a chemically characterized extract of P. acuminata should be further developed to treat fungal diseases in fruits from an agro-ecological model.

scholarly journals PDTM-17. MiR-126, miR-369-5p AND miR-487b DRIVE PEDIATRIC GLIOBLASTOMA INVASION VIA KCNA1

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi190-vi191
Author(s):  
Yulun Huang ◽  
Lin Qi ◽  
Mari Kogiso ◽  
Yuchen Du ◽  
Frank Braun ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neurological Deficits ◽  
Integrated Analysis ◽  
Normal Brain ◽  
Tumor Cell Migration ◽  
Monolayer Cultures ◽  
Invasive Capacity ◽  
Resected Primary Tumor

Abstract Diffuse invasion is one of the key features that make GBM particularly difficult to treat. We hypothesize that direct comparison of matched invasive (GBMINV) and tumor core GBM cells (GBMTC) would facilitate the discovery of drivers of pediatric GBM (pGBM) invasion. However, GBMINV cells are extremely difficult to obtain from normal brain tissues because aggressive surgical resection of normal tissue carries the risk of serious neurological deficits. Most past and current studies on GBM invasion were and are forced to utilize the resected primary tumor masses. To overcome this barrier, we utilized a panel of 6 pediatric patient tumor-derived orthotopic xenograft (PDOX) mouse models to isolate matching pairs of GBMTC cells and GBMINV cells and confirmed a significantly elevated invasive capacity in GBMINV cells both in vitro and in vivo. Global profiling of 768 human microRNA using a real-time PCR-based Taqman system identified 23 microRNAs were upregulated in the GBMINV cells in at least 4 of the 6 pGBM models as compared with the matching GBMTC cells. We subsequently showed that silencing the top three miRNAINV, miR-126, miR-369-5p, and miR-487b, suppressed tumor cell migration in vitro (both as neurospheres and monolayer cultures) without affecting cell proliferation, and blocked pGBM invasion in mouse brains. Integrated analysis of the mRNA profiling of the same set of GBMTC and GBMINV cells revealed the affected signaling pathways and identified KCNA1 as the sole common computational target gene of the three miRNAINV. Treatment of three pairs of GBMTC and GBMINV cells with two KCNA1 inhibitors, ADWX1 and Agitoxin 2, caused significant suppression of pGBM cell migration in vitro. In conclusion, this study revealed an intrinsically elevated invasive phenotype in GBMINV cells, identified miR-126, -369-5p, and -487b as novel drivers of pGBM invasion, and characterized KCNA1 as a potential therapeutic target for arresting pGBM invasion.

scholarly journals SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling

2017 ◽  
Vol 121 (6) ◽  
pp. 636-649 ◽  
Author(s):  
Xiaolong Zhu ◽  
Sha Ding ◽  
Cong Qiu ◽  
Yanna Shi ◽  
Lin Song ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Developmental Disorders ◽  
Interaction Mechanism ◽  
Growth Factor Receptor ◽  
Vascular Diseases ◽  
Cell Interaction ◽  
Protein Signaling

Rationale: The highly conserved NOTCH (neurogenic locus notch homolog protein) signaling pathway functions as a key cell–cell interaction mechanism controlling cell fate and tissue patterning, whereas its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders. Objective: The aim of this study was to investigate the role of SUMOylation in endothelial NOTCH signaling and angiogenesis. Methods and Results: Endothelial SENP1 (sentrin-specific protease 1) deletion, in newly generated endothelial SENP1 (the major protease of the SUMO system)–deficient mice, significantly delayed retinal vascularization by maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and immunoprecipitation analyses and dual-luciferase assays of natural and SUMO-conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized it for translocation to the nucleus where it functions as a cotranscriptional factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn suppressed VEGF (vascular endothelial growth factor) receptor signaling and angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro angiogenesis assays. Conclusions: These results establish reversible NOTCH1 SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic signaling; SENP1 acts as a critical intrinsic mediator of this process. These findings may apply to NOTCH-regulated biological events in nonvascular tissues and provide a novel therapeutic strategy for vascular diseases and tumors.

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