SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline

Intrathecal administration enables central nervous system delivery of drugs that do not bypass the blood-brain barrier. Systemic administration of hypertonic saline (HTS) enhances delivery of intrathecal therapeutics into the neuropil, but its effect on solute clearance from the brain remains unknown. Here, we developed a dynamic in vivo single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging platform to study the effects of HTS on whole-body distribution of the radiolabeled tracer (99)mTc-diethylenetriaminepen-taacetic acid (DTPA) administered through intracisternal, intrastriatal, or intravenous route in anesthetized rats. Co-administration of systemic HTS increased intracranial exposure to intracisternal (99)mTc-DTPA by similar to 80% during imaging. In contrast, HTS had minimal effects on brain clearance of intrastriatal (99)mTc-DTPA. In sum, SPECT/CT imaging presents a valuable approach to study glymphatic drug delivery. Using this methodology, we show that systemic HTS increases intracranial availability of cerebrospinal fluid-administered tracer, but has marginal effects on brain clearance, thus substantiating a simple, yet effective strategy for enhancing intrathecal drug delivery to the brain.Peer reviewe

The Glymphatic System (En)during Inflammation

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival.</p

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus—A joint EAACI‐EANO position paper

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE‐mediated diseases and glioma. Allergic disease stems from a Th2‐biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour‐immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro‐Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult‐type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune–glioma interactions to ultimately improve patient prognosis and survival