DICAM promotes T17 lymphocyte trafficking across the blood-brain barrier during autoimmune neuroinflammation.

The migration of circulating leukocytes into the central nervous system (CNS) is a key driver of multiple sclerosis (MS) pathogenesis. The monoclonal antibody natalizumab proved that pharmaceutically obstructing this process is an effective therapeutic approach for treating relapsing-remitting MS (RRMS). Unfortunately, the clinical efficacy of natalizumab is somewhat offset by its incapacity to control the progressive forms of MS (PMS) and by life-threatening side effects in RRMS rising from the expression of its molecular target, very late antigen 4 (VLA4), on most immune cells and consequent impairment of CNS immunosurveillance.

Adult Medulloblastoma Demographic, Tumor and Treatment Impact since 2006: A Canadian University Experience.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017.

Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease.

Purpose: Corticotroph tumor progression (CTP) or Nelson's syndrome (NS) can occur in patients with Cushing's disease (CD) following bilateral adrenalectomy. It has rarely been observed in patients treated with long-term medical therapy for persistent CD. Osilodrostat (LCI699) is a new steroidogenesis inhibitor of 11β-hydroxylase (CYP11β1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217).

Interleukin-26, preferentially produced by T17 lymphocytes, regulates CNS barrier function.

Objective: To investigate the involvement of interleukin (IL)-26 in neuroinflammatory processes in multiple sclerosis (MS), in particular in blood-brain barrier (BBB) integrity.

Methods: Expression of IL-26 was measured in serum, CSF, in vitro differentiated T helper (T) cell subsets, and postmortem brain tissue of patients with MS and controls by ELISA, quantitative PCR, and immunohistochemistry. Primary human and mouse BBB endothelial cells (ECs) were treated with IL-26 in vitro and assessed for BBB integrity.

Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers.

The presence of B lymphocyte-associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated.

Morbidity Rate of the Retrosigmoid versus Translabyrinthine Approach for Vestibular Schwannoma Resection.

Background And Objectives: Controversy related to the choice of surgical approach for vestibular schwannoma (VS) resection remains. Whether the retrosigmoid (RS) or translabyrinthine (TL) approach should be performed is a matter of debate. In the context of a lack of clear evidence favoring one approach, we conducted a retrospective study to compare the morbidity rate of both surgical approaches.

Eustachian Tube Obliteration and its Effect on Rhinoliquorrhea in Translabyrinthine Vestibular Schwannoma Excision.

Objective: Rhinoliquorrhea is defined as a cerebrospinal fluid leakage from the nose. Our objective in this study is to determine the reduction of rhinoliquorrhea rates by Eustachian tube (ET) obliteration in the context of a translabyrinthine approach performed following vestibular schwannoma (VS) excision.

Materials And Methods: This is a prospective study achieved in a tertiary-care center where the chart review revealed 94 VS operated by the translabyrinthine approach between 2009 and 2015.

Long-term results of radiosurgery for cerebral arteriovenous malformations.

Background: Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM).

Objective: To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates.

Methods: We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy.

A comparison of two doses of mannitol on brain relaxation during supratentorial brain tumor craniotomy: a randomized trial.

Background: Twenty percent mannitol is widely used to reduce brain bulk and facilitate the surgical approach in intracranial surgery. However, a dose-response relationship has not yet been established. In this study, we compared the effects of 0.

Role of Ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions.

Objective: Blood-derived myeloid antigen-presenting cells (APCs) account for a significant proportion of the leukocytes found within lesions of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). These APCs along with activated microglia are thought to be pivotal in the initiation of the central nervous system (CNS)-targeted immune response in MS and EAE. However, the exact molecules that direct the migration of myeloid cells from the periphery across the blood-brain barrier (BBB) remain largely unknown.

Quality of life following hemicraniectomy for malignant MCA territory infarction.

Objective: Decompressive hemicraniectomy (DH) has been shown to reduce mortality in patients with malignant middle cerebral artery (MCA) territory infarction. However, many patients survive with moderate-to-severe disability and controversy exists as to whether this should be considered good outcome. To answer this question, we assessed the quality of life (QoL) of patients after DH for malignant MCA territory infarction in our milieu.

Superficial cervical plexus block for transitional analgesia in infratentorial and occipital craniotomy: a randomized trial.

Background: In this study, we compared the quality of transitional analgesia provided by bilateral superficial cervical plexus block (SCPB) or morphine following a remifentanil-based anesthesia for infratentorial or occipital craniotomy.

Methods: In this randomized controlled and double-blind study, 30 patients scheduled for infratentorial or occipital craniotomy were divided randomly into two groups: group morphine (morphine 0.1 mg·kg⁻¹ iv after dural closure and a SCPB performed with 20 mL of 0.

Decompressive craniectomy is not an independent risk factor for communicating hydrocephalus in patients with increased intracranial pressure.

Background: It was recently suggested that communicating hydrocephalus is an almost universal finding after hemicraniectomy and that early cranioplasty may prevent the need for permanent cerebrospinal fluid diversion in these patients.

Objective: To conduct a study in an attempt to verify these findings.

Methods: The medical records of all patients who underwent decompressive craniectomy for medically refractory elevated intracranial pressure between 2001 and 2009 were retrospectively reviewed.

Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts.

Among the natural products shown to possess chemopreventive and anticancer properties, curcumin is one of the most potent. In the current study, we investigated the effects of this natural product on the growth of human glioma U-87 cells xenografted into athymic mice. We show here that curcumin administration exerted significant anti-tumor effects on subcutaneous and intracerebral gliomas as demonstrated by the slower tumor growth rate and the increase of animal survival time.

The effect of sedation on intracranial pressure in patients with an intracranial space-occupying lesion: remifentanil versus propofol.

Background: In this study, we compared the effect of light sedation with remifentanil versus propofol on intracranial (ICP) and cerebral perfusion pressure (CPP) of patients undergoing stereotactic brain tumor biopsy under regional anesthesia.

Methods: This was a prospective, open-label, randomized, and controlled study. Forty patients undergoing stereotactic brain tumor biopsy under regional anesthesia were randomized into two groups to receive remifentanil or propofol titrated to a level of four on the modified Assessment of Alertness/Sedation Scale.

Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion.

In recent clinical observation, the growth of endothelial tumors, such as hemangiomas of infancy, was repressed by the non-selective beta-adrenergic antagonist propranolol possibly through targeting of the vascular endothelial compartment. As human brain microvascular endothelial cells (HBMEC) play an essential role as structural and functional components in tumor angiogenesis, we assessed whether propranolol could target HBMEC's in vitro angiogenic properties. We found that biopsies from human glioblastoma as well as from experimental brain tumor-associated vasculature expressed high levels of the beta2-adrenergic receptor, suggesting adrenergic adaptative processes could take place during tumor vascularization.

The diet-derived sulforaphane inhibits matrix metalloproteinase-9-activated human brain microvascular endothelial cell migration and tubulogenesis.

Human brain microvascular endothelial cells (HBMECs) play an essential role as structural and functional components of the blood-brain barrier (BBB). While disruption of the BBB by the brain tumor-secreted matrix metalloproteinase-9 (MMP-9) favors tumor invasion, the role and regulation of MMP-9 secretion by HBMEC themselves in response to carcinogens or brain tumor-derived growth factors has received little attention. Our study delineates a unique brain endothelial phenotype in that MMP-9 secretion is increased upon phorbol 12-myristate 13-acetate (PMA) treatment of HBMEC.

Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system.

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups.

Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis.

The blood-brain barrier (BBB) restricts molecular and cellular trafficking between the blood and the CNS. Although astrocytes are known to control BBB permeability, the molecular determinants of this effect remain unknown. We show that angiotensinogen (AGT) produced and secreted by astrocytes is cleaved into angiotensin II (AngII) and acts on type 1 angiotensin receptors (AT1) expressed by BBB endothelial cells (ECs).