surgical-technique-for-spinal-cord-delivery-therapies-demonstration

Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs

This is a  compact visual description of a combination of surgical technique and device  for the  delivery of (gene and cell) therapies into the spinal ...

modeling-neonatal-intraventricular-hemorrhage-through

Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin

Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and ...

Emory University

University of Kentucky

University of Texas

CNS Plasticity in Injury and Disease.

Cerebral venous sinus thrombosis after cranial surgery in children.

Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present a unique report of a neonate with SAH from anterior inferior cerebellar artery (AICA) aneurysm rupture that was successfully treated with Onyx embolization. This case report demonstrates the utility of Onyx embolization for posterior circulation aneurysms in neonates and the successful management of SAH in this population.

Onyx embolization of a ruptured anterior inferior cerebellar artery in a neonate.

The authors sought to determine if hydrocephalus caused a proinflammatory state within white matter as is seen in many other forms of neonatal brain injury. Common causes of hydrocephalus (such as trauma, infection, and hemorrhage) are inflammatory insults themselves and therefore confound understanding of how hydrocephalus itself affects neuroinflammation. Recently, a novel animal model of hydrocephalus due to a genetic mutation in the Ccdc39 gene has been developed in mice. In this model, ciliary dysfunction leads to early-onset ventriculomegaly, astrogliosis, and reduced myelination. Because this model of hydrocephalus is not caused by an antecedent proinflammatory insult, it was utilized to study the effect of hydrocephalus on inflammation within the white matter of the corpus callosum.

Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice.

Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.

A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus.

Republished: A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus.

Neonatal intraventricular hemorrhage (IVH) leads to posthemorrhagic hydrocephalus (PHH), brain injury, and long-term disability. Current therapy for IVH is based on treating PHH but does not address the underlying brain injury. In order to develop pharmacological treatment for IVH, there must be a better understanding of the underlying pathology of this disease. This study was designed to determine the time course of the acute inflammation and oxidative stress that may underlie the progressive pathology of IVH. The authors sought to understand the temporal relationships among inflammation, oxidative stress, and white matter pathology in a rat model of IVH.

Acute brain inflammation, white matter oxidative stress, and myelin deficiency in a model of neonatal intraventricular hemorrhage.

Oligodendrocyte progenitor cells (OPCs) in the infant brain give rise to mature oligodendrocytes that myelinate CNS axons. OPCs are particularly vulnerable to oxidative stress that occurs in many forms of brain injury. One common cause of infant brain injury is neonatal intraventricular hemorrhage (IVH), which releases blood into the CSF and brain parenchyma of preterm infants. Although blood contains the powerful oxidant hemoglobin, the direct effects of hemoglobin on OPCs have not been studied. We utilized a cell culture system to test if hemoglobin induced free radical production and mitochondrial dysfunction in OPCs. We also tested if phenelzine (PLZ), an FDA-approved antioxidant drug, could protect OPCs from hemoglobin-induced oxidative stress. OPCs were isolated from Sprague Dawley rat pups and exposed to hemoglobin with and without PLZ. Outcomes assessed included intracellular reactive oxygen species levels using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent dye, oxygen consumption using the XFe96 Seahorse assay, and proliferation measured by BrdU incorporation assay. Hemoglobin induced oxidative stress and impaired mitochondrial function in OPCs. PLZ treatment reduced hemoglobin-induced oxidative stress and improved OPC mitochondrial bioenergetics. The effects of hemoglobin and PLZ on OPC proliferation were not statistically significant, but showed trends towards hemoglobin reducing OPC proliferation and PLZ increasing OPC proliferation (P=0.06 for both effects). Collectively, our results indicate that hemoglobin induces mitochondrial dysfunction in OPCs and that antioxidant therapy reduces these effects. Therefore, antioxidant therapy may hold promise for white matter diseases in which hemoglobin plays a role, such as neonatal IVH.

Hemoglobin induces oxidative stress and mitochondrial dysfunction in oligodendrocyte progenitor cells.

Cerebral venous sinus thrombosis (VST) is a complication of head injury and can be secondary to sinus compression by depressed skull fractures. Fracture elevation is a treatment option for VST secondary to extrinsic compression, but conservative management may also be effective. Venous sinuses can also be lacerated from skull fractures, resulting in epidural or subdural hematomas. The authors presented a case of sagittal sinus injury and thrombosis from a depressed skull fracture that caused a subgaleal hematoma. The injury was successfully managed conservatively.

ArticleTotal : 2	Year
Publication title Cited by 24	2012
Publication title Cited by 12	2022

Article	Year
CNS Plasticity in Injury and Disease. Neural plasticity\| PubMed ID: 26881092	2016
Cerebral venous sinus thrombosis after cranial surgery in children. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery\| PubMed ID: 29143116	2018
Onyx embolization of a ruptured anterior inferior cerebellar artery in a neonate. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery\| PubMed ID: 30203392	2019
Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice. Journal of neurosurgery. Pediatrics\| PubMed ID: 32032950	2020
A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus. BMJ case reports\| PubMed ID: 32132100	2020
Republished: A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus. Journal of neurointerventional surgery\| PubMed ID: 32184274	2020
Acute brain inflammation, white matter oxidative stress, and myelin deficiency in a model of neonatal intraventricular hemorrhage. Journal of neurosurgery. Pediatrics\| PubMed ID: 32858507	2020
Hemoglobin induces oxidative stress and mitochondrial dysfunction in oligodendrocyte progenitor cells. Translational research : the journal of laboratory and clinical medicine\| PubMed ID: 33460824	2021
Pediatric skull fracture with injury and thrombosis of the superior sagittal sinus: illustrative case. Journal of neurosurgery. Case lessons\| PubMed ID: 35855207	2022

Brandon A. Miller

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