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Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.

PURPOSE: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobi … cus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recove …

CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges.

1. The effects of intravenously administered 5-HT1B receptor agonists were examined on c-fos like immunoreactivity, an indicator of neuronal activation, within the brain stem. C-fos was induced by injecting an algesic, vasoconstrictor substance (0.3 ml of autologous blood) or a pro-inflammatory molecule, carrageenin (1 mg in 0.1 ml saline) into the cisterna magna of pentobarbitone-anaesthetized Sprague-Dawley rats and was visualized in serial sections (50 micrometers) by use of a polyclonal antiserum. 2. As previously reported, the injection of blood caused significant labelling within laminae…

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis.

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with ste…

Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage.

Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca2+ channels (VDCCs) encoded by the gene CaV 2.3. Us

Posterior fossa lesions associated with neuropsychiatric symptomatology.

We reviewed 7 cases with posterior fossa structural abnormalities (3 tumors, 2 megacisterna magna and 2 Dandy-Walker syndrome) presenting with neuropsychiatric symptomatology. Derangement in the balance of dopamine, serotonin and noradrenergic networks has been implicated in the pathogenesis of schizophrenia, affective and even personality disorders. Disruption of the cerebellar output to mesial dopaminergic areas, locus coeruleus and raphe nuclei, or deafferentation of the thalamolimbic circuits by a cerebellar lesion may lead to behavioral changes. Seven patients (pts) (comprising 4 men and …

Modified approach for the selective treatment of temporal lobe epilepsy: transsylvian-transcisternal mesial en bloc resection.

OBJECT: The authors propose a novel surgical approach for amygdalohippocampectomy (AH) in patients with temporal lobe epilepsy. Via a transsylvian-transcisternal route, the parahippocampal gyrus is directly exposed from its medial aspect, thus allowing a standardized en bloc resection of the temporomesial epileptogenic structures--the amygdala, anterior hippocampus, parahippocampal gyrus, and subiculum. Additional anatomical studies have been performed for standardization of this approach. METHODS: From 1990 to 1996, 32 patients presenting with medically intractable mesial temporal lobe epile

Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX.

Mutations in the Senataxin gene (SETX) are associated with autosomal recessive ataxia-ocular apraxia 2 (AOA2) and autosomal dominant juvenile ALS (ALS4). Here, the authors describe novel homozygous missense mutations in SETX, M274I, and R1294C, found in two siblings with ataxia, peripheral neuropathy, and increased serum alpha-fetoprotein level and three other siblings with heterozygous missense mutations who were neurologically asymptomatic. The results demonstrate that the double missense mutations are responsible for AOA2 but not for ALS4.

Germline and mosaic mutations of FLN1 in men with periventricular heterotopia.

OBJECTIVE: To describe the phenotypic spectrum and genetics of periventricular nodular heterotopia (PNH) caused by FLN1 mutations in four men. BACKGROUND: X-linked PNH caused by FLN1 mutations (MIM #300049) implies prenatal or early postnatal lethality in boys and 50% recurrence risk in daughters of affected women. METHODS: Clinical examination, cognitive testing, MRI, and mutation analysis (denaturing high-performance liquid chromatography and direct sequencing) on blood lymphocytes and single hair roots were performed for nine affected individuals, including three men. Neuropathologic stud

Intracisternal TRH analog induces Fos expression in gastric myenteric neurons and glia in conscious rats.

Activation of gastric myenteric cells by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368, at a dose inducing near maximal vagal cholinergic stimulation of gastric functions, was investigated in conscious rats. Fos immunoreactivity was assessed in gastric longitudinal muscle-myenteric plexus whole mount preparations 90 min after intracisternal injection. Fos-immunoreactive cells were rare in controls (~1 cell/ganglion), whereas intracisternal RX-77368 (50 ng) increased the number to 24.8 +/- 1.8 and 26.8 +/- 2.2 cells/ganglion in the corpus and antrum,

Blended Phenotype Involving FBN1 and Novel PIGL Variants of Uncertain Significance: A Prenatal Case Report.

Genetic disorders presenting during the prenatal period are often complex, with overlapping phenotypes that pose significant diagnostic chal … nephrosis and hydroureter, absent nasal bone, flat midface, micrognathia, and low-set ears, dilated cisterna magna, vermian agenesis, and Blake's pouch cyst. The fetal whole-genome sequence was found to harbor an autosomal dominant, heterozygous VUS in the FBN1 gene at exon 18 associated with MFS and ACMICD. It also had an autosomal recessive homozygous VUS, pos …

Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results.

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50

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… The dose was administered in a volume of 6.5 μl via the cisterna magna and was compared with the effects of IT administration of equal volumes of vehicle or rat immunuglobulin-G2a (IgG2a) control antibodies (vehicle, n = 22; isotype antibody, n = 23; anti-PD1, n = 23). … Solution was dispensed slowly over 2 min into the cisterna magna, and the needle was then withdrawn. The mice were then resuscitated from anesthesia. …

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

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… /cisterna magna combined. The study uses two rAAV.rh8 vectors delivering the HEXA or HEXB transgene. Results from these trials are pending. CD is an autosomal recessive inherited progressive neurodegenerative disease hallmarked by spongiform degeneration and elevation of N-acetylaspartate (NAA). …

Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.

Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients' lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field s

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… Taghian T Marosfoi MG Puri AS Cataltepe OI King RM Diffie EB A safe and reliable technique for CNS delivery of AAV vectors in the cisterna magna Mol Ther 2020 28 2 411 21 10.1016/j.ymthe.2019.11.012 31813800 PMC7002897 Taghian T, Marosfoi MG, Puri AS, Cataltepe OI, King RM, Diffie EB, et al. … A safe and reliable technique for CNS delivery of AAV vectors in the cisterna magna. Mol Ther. 2020;28(2):411–21. 31813800 10.1016/j.ymthe.2019.11.012 PMC7002897 52. …

Лазерно-приводимые кортики в мышах в качестве модели прогрессивной многоклерозной патологии.

Справочная информация: В нынешних моделях склероза (MS) для животных основное внимание уделяется воспалению белой материи, отражающему раннее заболевание. Однако прогрессивные MS (PMS) характеризуются кортикальной патологией, включая подпиальное демиэлирование, хроническое менингеальное воспаление и микроглиальную активацию, которые недопредставлены в существующих моделях. В то время как альтернативные модели мыши воспроизводят релапсирующий фенотип и серую патологию материи, патология часто рассеивается по мозгу, что осложняет анализ конкретных участков поражения. Методы: Для устранения этого

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… A 30-gauge needle (bent 55° with a 2 mm tip) was attached to a 50 μL Hamilton syringe to perform an intrathecal injection into the cisterna magna. …

Ataxia-Telangiectasia and Associated Bronchiectasis: Case Report and Literature Review.

Ataxia-telangiectasia is a rare, autosomal recessive primary immunodeficiency caused by mutations in the ATM gene on chromosome 11, which encodes a serine-threonine kinase essential for the recognition and repair of DNA double-strand breaks. The disease is characterized by progressive neurological impairment, immunological dysfunction, and an increased susceptibility to recurrent infections and malignancies. Pulmonary involvement represents a major source of morbidity and frequently arises from chronic infections, aspiration, and impaired airway clearance, ultimately leading to the development

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… In the posterior cranial fossa, there was widening of the pericerebellar space (cisterna magna and ambient cistern), enlargement of the fourth ventricle, and deepening of the cerebellar cortical sulci. …

Протеомический анализ показывает, что потенциальные молекулы могут выступать посредником в кортикальной патологии и выявлять возможные биомаркеры в животной модели множественного склероза.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой сложное нейродегенеративное заболевание, характеризующееся повторяющимися вспышками, обезвоживанием, повреждением аксона и последующей потерей функции. MS представляет широкий спектр клинических курсов, прогрессивные формы которых приводят к необратимой неврологической инвалидности. Кортикальные демиелионирующие повреждения имеют ключевое значение для патологии этих прогрессивных форм, и в последние десятилетия они приобретают решающее значение в силу их тесной связи с физической инвалидностью и когнитивным упадком. Несмотря на это, механ

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… An insulin needle (27G × ½") was inserted into the cisterna magna, allowing us to obtain a maximum of 100 μL per animal. The samples were maintained on ice until centrifugation at 2,000 g for 10 min at 4°C. …

Disorders of the Spinal Cord

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… Cisterna magna puncture is contraindicated given the likelihood of inadvertent puncture of the spinal cord. Lumbar CSF analysis may show chronic inflammation, but is frequently normal. …

Diseases of the Nervous System

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Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

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… These in vitro findings are augmented by in vivo experiments that demonstrate injecting TFAM alone into the cisterna magna of rats causes significantly increased expression of MCP-1, IL-1β, IL-6, TNF, and NF-κB inhibitor alpha in the frontal cortex and hippocampus (Schindler et al., 2018). …

Clinical development of gene therapy: results and lessons from recent successes.

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerativ

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… For example, infusion of the vector into the cisterna magna (for delivery into cerebrospinal fluid) or use of vectors that can cross the blood brain barrier is being explored to replace conventional intracranial injections. 82 , 83 Finally, promising results on correction of motor neurons in infant children …