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Cell Feb 2023The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage,...
The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highly similar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSF production from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinase SPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.
Topics: Humans; Blood-Brain Barrier; Brain; Choroid Plexus; Hydrocephalus; Immunity, Innate; Cytokine Release Syndrome
PubMed: 36803604
DOI: 10.1016/j.cell.2023.01.017 -
Neuron May 2023Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An...
Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K] and triggered cytosolic calcium activity in ChP epithelial cells, which was followed by NKCC1 activation. ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity. These data demonstrate that intraventricular blood triggered a trans-choroidal, NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF [K] fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to mitigate intracranial fluid accumulation following hemorrhage.
Topics: Humans; Choroid Plexus; Hydrocephalus; Cerebral Hemorrhage
PubMed: 36893755
DOI: 10.1016/j.neuron.2023.02.020 -
Ophthalmologica. Journal International... 2023Suprachoroidal hemorrhage (SCH) refers to the accumulation of blood in the suprachoroidal space, a relatively uncommon but significant complication that can occur... (Review)
Review
Suprachoroidal hemorrhage (SCH) refers to the accumulation of blood in the suprachoroidal space, a relatively uncommon but significant complication that can occur spontaneously, during ophthalmic surgery, or as a consequence of ocular trauma. If left undiagnosed and untreated, SCH can lead to severe vision loss or even blindness. Therefore, it is crucial for ophthalmologists to have a thorough understanding of this complication, taking proactive measures to prevent it during surgery and being knowledgeable about effective management strategies for patients with SCH. This review article aimed to provide a comprehensive overview of SCH, covering its risk factors, diagnostic approaches, and the best practices for its management. By enhancing awareness and knowledge in this area, we can improve patient outcomes and minimize the impact of SCH in ophthalmic practice.
Topics: Humans; Choroid Hemorrhage; Vitrectomy; Risk Factors; Visual Acuity; Ophthalmology
PubMed: 37660688
DOI: 10.1159/000533937 -
Translational Pediatrics Apr 2021Cranial ultrasound (CUS) is an extremely valuable tool to evaluate the brain during the first year of life, in experienced hands. It is the initial screening imaging... (Review)
Review
Cranial ultrasound (CUS) is an extremely valuable tool to evaluate the brain during the first year of life, in experienced hands. It is the initial screening imaging tool to evaluate the infants' brain and complementary to the use of computed tomography (CT) and magnetic resonance imaging (MRI). It is an accessible, inexpensive and harmless technique that can be used bedside as frequently as needed. The aim of this article is to provide a guide for beginners about the indications, basic technical parameters, scanning technique, standardized planes, common variants and the most frequent abnormal findings visualized with this technique. This article will explain a systematic technique to adequately visualize and document all the relevant intracranial structures, using the anterior fontanelle, mastoid fontanelle and Doppler ultrasound. The variants described in this review include the normal sulcation of the premature baby, the peritrigonal echogenic "blush", lenticulostriate vasculopathy (LSV), benign enlargement of the subrarachnoid space in infancy, asymmetric lateral ventricles, connatal cysts, cavum septum pellucidum (CSP), cavum vergae (CV), cavum velum interpositum, megacisterna magna and choroid plexus cysts. This article will describe the sonographic appearance of different types of intracranial hemorrhage of the preterm and term baby, periventricular leukomalacia (PVL), central and peripheral hypoxic-ischemic events of the term baby, neonatal arterial infarction, cerebro-venous sinus thrombosis, congenital and neonatal cerebral infections, hydrocephalus, intracranial solid and cystic masses, and congenital brain malformations.
PubMed: 34012859
DOI: 10.21037/tp-20-399 -
EBioMedicine Apr 2022Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular... (Review)
Review
Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular and subarachnoid hemorrhage, traumatic brain injuries, brain tumors, craniectomy or may be idiopathic, as in the case of normal pressure hydrocephalus. Irrespective of its prevalence and significant impact on quality of life, neurosurgeons still rely on invasive cerebrospinal fluid shunt systems for the treatment of hydrocephalus that are exceptionally prone to failure and/or infection. Further understanding of this process at a molecular level, therefore, may have profound implications for improving treatment and quality of life for millions of individuals worldwide. The purpose of this article is to review the current research landscape on hydrocephalus with a focus on recent advances in our understanding of cerebrospinal fluid pathways from an evolutionary, genetics and molecular perspective.
Topics: Heart Ventricles; Humans; Hydrocephalus; Infant; Quality of Life; Subarachnoid Hemorrhage
PubMed: 35306341
DOI: 10.1016/j.ebiom.2022.103931 -
Expert Opinion on Therapeutic Targets Jun 2020Recent data have implicated inflammation of the cerebrospinal fluid spaces after subarachnoid, intraventricular, and intracerebral hemorrhage to be a critical driver of... (Review)
Review
Recent data have implicated inflammation of the cerebrospinal fluid spaces after subarachnoid, intraventricular, and intracerebral hemorrhage to be a critical driver of multiple secondary brain injuries such as hydrocephalus, cerebral edema, and vasospasm. While TLR4-dependent reparative inflammation is an important protective response that can eliminate physical irritants and damaged cells, sustained or inappropriately triggered inflammation can initiate or propagate disease.: We review recent advances in our understanding of how TLR4, including its upstream damage-associated molecular patterns and its downstream MyD88-dependent and independent signaling pathways, contributes to hemorrhage-induced inflammation in numerous brain diseases. We discuss prospects for the pharmacotherapeutic targeting of TLR4 in these disorders, including the use of repurposed FDA-approved agents.: TLR4 inhibitors with good blood-brain-barrier (BBB) penetration could be useful adjuncts in post-hemorrhagic hydrocephalus and multiple other diseases associated with brain hemorrhage and inflammation.
Topics: Animals; Blood-Brain Barrier; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Humans; Inflammation; Molecular Targeted Therapy; Signal Transduction; Toll-Like Receptor 4
PubMed: 32249624
DOI: 10.1080/14728222.2020.1752182 -
Indian Journal of Ophthalmology Jun 2020The present review describes the posterior segment complications following surgical management of glaucoma. Although the majority of glaucoma cases are managed... (Review)
Review
The present review describes the posterior segment complications following surgical management of glaucoma. Although the majority of glaucoma cases are managed medically, still a large number of patients may require surgery. Moreover, with the advent of newer surgical techniques and adjuncts, encountering retinal complications post-surgery is not uncommon. The incidence, signs, management, and prognosis of common complications such as anesthesia-related retinal toxicity, vitreous loss, suprachoroidal hemorrhage, serous choroidal detachment, hypotonic maculopathy, vitreous hemorrhage, retinal detachment and endophthalmitis will be discussed in detail. Awareness of these complications is necessary as their proper and timely management can save vision in an already compromised eye.
Topics: Choroid Hemorrhage; Glaucoma; Humans; Ophthalmologic Surgical Procedures; Postoperative Complications; Retinal Detachment; Retrospective Studies; Vitrectomy; Vitreous Hemorrhage
PubMed: 32461411
DOI: 10.4103/ijo.IJO_1040_19