scholarly journals A Novel Model of Acquired Hydrocephalus for Evaluation of Neurosurgical Treatments

Author(s):  
James (Pat) Mcallister ◽  
Michael Talcott ◽  
Albert M. Isaacs ◽  
Leandro Castaneyra-Ruiz ◽  
Sarah H. Zwick ◽  
...  

Abstract Background.Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in ways similar to gyrencephalic species and whose size is not amenable to evaluation of clinically-relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs. Methods. Acquired hydrocephalus was induced in 30-35-day old pigs by percutaneous intracisternal injections of kaolin. Intracisternal and intraventricular injections of autologous blood was attempted in 2 cases to induce post-hemorrhagic hydrocephalus. Magnetic resonance imaging (MRI) was employed to evaluate the progression of ventriculomegaly and plan the surgical implantation of ventriculoperitoneal shunts at approximately 1–4 weeks post-kaolin. Behavioral and neurological status was assessed continuously. Results. Bilateral ventriculomegaly occurred post-induction and was characterized by enlargement of all portions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in basal cisterns but the cisterna magna was patent. In 14 untreated hydrocephalic animals, mean total ventricular volumes were 6786 ± 4336 SD mm3 at 17–57 days post-kaolin, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 in sham controls. Consistent with human hydrocephalus, intermittent disruption of the ventricular zone of the lateral ventricles was characterized by loss of multiciliated ependymal cells and the appearance of reactive astrocytes. Past the post-induction recovery period, untreated pigs were asymptomatic in spite of exhibiting mild-moderate ventriculomegaly. Shunted animals developed ataxia and lethargy only when obstruction of the ventricular catheter and/or distal valve occurred. Conclusions. Mechanical induction of acquired hydrocephalus produces a reliable in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.

Author(s):  
Filippo Casoni ◽  
Laura Croci ◽  
Francesca Vincenti ◽  
Paola Podini ◽  
Luca Massimino ◽  
...  

ABSTRACTThe choroid plexus (ChP) is a secretory tissue that produces cerebrospinal fluid (CSF) and secretes it into the ventricular system. CSF flows from the lateral to the third ventricle, and then to the fourth ventricle through the cerebral aqueduct. Recent studies have uncovered new, active roles for this structure in the regulation of neural stem cell maintenance and differentiation into neurons. Zfp423, encoding a Kruppel-type zinc finger transcription factor essential for cerebellar development and mutated in rare cases of cerebellar vermis hypoplasia / Joubert syndrome and other ciliopathies, is expressed in the hindbrain roof plate (RP), from which the IV ventricle ChP arises, and in mesenchymal cells giving rise to the stroma and leptomeninges. Zfp423 mutants display a marked reduction of the hindbrain ChP (hChP), which fails to express key markers of its secretory function and genes implicated in its development and maintenance (Lmx1a, Otx2). The mutant hChP displays a complete lack of multiciliated ependymal cells. A transcriptome analysis conducted at the earliest stages of hChP development and subsequent validations demonstrate that the mutant hChp displays a strong deregulation of pathways involved in early hindbrain patterning and multiciliated cell fate specification. Our results propose Zfp423 as a master gene and one of the earliest known determinants of hChP development.


2007 ◽  
Vol 22 (4) ◽  
pp. 1-8 ◽  
Author(s):  
Kristen Upchurch ◽  
Murisiku Raifu ◽  
Marvin Bergsneider

Object Patients with symptomatic isolated fourth ventricle and multicompartmentalized hydrocephalus benefit from operative treatment, but the optimal surgical approach and technique have yet to be established. The authors report on their experience with the treatment of symptomatic adult patients by endoscope-assisted placement of a fourth ventricle shunt catheter via a frontal transventricular approach. Methods The authors describe a retrospective series of four patients treated for isolated fourth ventricle. The surgical technique is described in detail: use of a flexible endoscope with dual-port intraventricular access for direct visualization and for mechanical manipulation of a multiperforated panventricular catheter guided by frameless stereotaxy. The transventricular approach allowed optimal catheter placement within the fourth ventricle. The use of the flexible endoscope permitted the neurosurgeon to use the endoscope as a tool to guide the ventricular catheter tip within the third ventricle and through the cerebral aqueduct. Clinical outcomes demonstrated neurological and radiographically verified improvement in all patients. Conclusions The endoscope-assisted dual-port technique provides a solution to the technical difficulties of fourth ventricle shunt placement. The multiple advantages of this technique include a single ventricular catheter shunt system that equalizes ventricular pressures, a frontal location for the ventricular catheter that facilitates valve placement and programming, and ventricular catheter placement within the fourth ventricle that does not allow the catheter to impinge on the fourth ventricle floor and makes the catheter less prone to obstruction.


2020 ◽  
pp. 1-9 ◽  
Author(s):  
Alberto Feletti ◽  
Alessandro Fiorindi ◽  
Vincenzo Lavecchia ◽  
Rafael Boscolo-Berto ◽  
Elisabetta Marton ◽  
...  

OBJECTIVEDespite the technological advancements of neurosurgery, the posterior part of the third ventricle has always been the “dark side” of the ventricle. However, flexible endoscopy offers the opportunity for a direct, in vivo inspection and detailed description of the posterior third ventricle in physiological and pathological conditions. The purposes of this study were to describe the posterior wall of the third ventricle, detailing its normal anatomy and surgical landmarks, and to assess the effect of chronic hydrocephalus on the anatomy of this hidden region.METHODSThe authors reviewed the video recordings of 59 in vivo endoscopic explorations of the posterior third ventricle to describe every identifiable anatomical landmark. Patients were divided into 2 groups based on the absence or presence of a chronic dilation of the third ventricle. The first group provided the basis for the description of normal anatomy.RESULTSThe following anatomical structures were identified in all cases: adytum of the cerebral aqueduct, posterior commissure, pineal recess, habenular commissure, and suprapineal recess. Comparing the 2 groups of patients, the authors were able to detect significant variations in the shape of the adytum of the cerebral aqueduct and in the thickness of the habenular and posterior commissures. Exploration with sodium fluorescein excluded the presence of any fluorescent area in the posterior third ventricle, other than the subependymal vascular network.CONCLUSIONSThe use of a flexible scope allows the complete inspection of the posterior third ventricle. The anatomical variations caused by chronic hydrocephalus might be clinically relevant, in light of the commissure functions.


1991 ◽  
Vol 75 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Atsushi Teramura ◽  
Robert Macfarlane ◽  
Christopher J. Owen ◽  
Ralph de la Torre ◽  
Kenton W. Gregory ◽  
...  

✓ Laser energy of 480 nm was applied in 1-µsec pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-µm fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood, 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-µsec pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.


1996 ◽  
Vol 270 (6) ◽  
pp. F1057-F1065 ◽  
Author(s):  
Y. H. Wang ◽  
S. C. Borkan

The 72-kDa heat stress protein (HSP-72) is an inducible cytoprotectant protein. Although transient renal ischemia in vivo induces HSP-72, it is not known whether prior heat stress protects renal epithelial cells from injury mediated by ATP depletion. To evaluate this hypothesis, opossum kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D-glucose in the absence of medium glucose, a maneuver that reduced cell ATP content to < 10% of the control value within 10 min and decreased cell survival. One day after 2 h of ATP depletion, OK cells previously exposed to heat stress (to induce accumulation of HSP-72) exhibited marked improvement in survival (a > 4-fold increase in total DNA), less uptake of vital dye, and less release of lactate dehydrogenase (LDH) than cells subjected to ATP depletion alone (23.0 +/- 1.6 vs. 34.1 +/- 1.2% of total LDH, respectively). Enhanced clonogenicity post-heat stress was completely prevented by cycloheximide and positively correlated with the steady-state content of HSP-72. In the recovery period after ATP depletion, cell ATP content, maximum mitochondrial ATP production rate, and total LDH activity were all significantly higher in cells with abundant HSP-72. Although the protective effects associated with heat stress are likely to be multifactoral, preserved cell metabolism and higher ATP content could enhance cellular repair processes after ATP depletion.


2019 ◽  
Vol 131 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Rajiv R. Iyer ◽  
Noah Gorelick ◽  
Karen Carroll ◽  
Ari M. Blitz ◽  
Sarah Beck ◽  
...  

OBJECTIVEVentricular shunt infection remains an issue leading to high patient morbidity and cost, warranting further investigation. The authors sought to create an animal model of shunt infection that could be used to evaluate possible catheter modifications and innovations.METHODSThree dogs underwent bilateral ventricular catheter implantation and inoculation with methicillin-sensitive Staphylococcus aureus (S. aureus). In 2 experimental animals, the catheters were modified with a polymer containing chemical “pockets” loaded with vancomycin. In 1 control animal, the catheters were polymer coated but without antibiotics. Animals were monitored for 9 to 11 days, after which the shunts were explanted. MRI was performed after shunt implantation and prior to catheter harvest. The catheters were sonicated prior to microbiological culture and also evaluated by electron microscopy. The animals’ brains were evaluated for histopathology.RESULTSAll animals underwent successful catheter implantation. The animals developed superficial wound infections, but no neurological deficits. Imaging demonstrated ventriculitis and cerebral edema. Harvested catheters from the control animal demonstrated > 104 colony-forming units (CFUs) of S. aureus. In the first experimental animal, one shunt demonstrated > 104 CFUs of S. aureus, but the other demonstrated no growth. In the second experimental animal, one catheter demonstrated no growth, and the other grew trace S. aureus. Brain histopathology revealed acute inflammation and ventriculitis in all animals, which was more severe in the control.CONCLUSIONSThe authors evaluated an animal model of ventricular shunting and reliably induced features of shunt infection that could be microbiologically quantified. With this model, investigation of pathophysiological and imaging correlates of infection and potentially beneficial shunt catheter modifications is possible.


2018 ◽  
Vol 17 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Alberto Feletti ◽  
Riccardo Stanzani ◽  
Matteo Alicandri-Ciufelli ◽  
Giuliano Giliberto ◽  
Matteo Martinoni ◽  
...  

AbstractBACKGROUNDDuring surgery in the posterior fossa in the prone position, blood can sometimes fill the surgical field, due both to the less efficient venous drainage compared to the sitting position and the horizontally positioned surgical field itself. In some cases, blood clots can wedge into the cerebral aqueduct and the third ventricle, and potentially cause acute hydrocephalus during the postoperative course.OBJECTIVETo illustrate a technique that can be used in these cases: the use of a flexible scope introduced through the opened roof of the fourth ventricle with a freehand technique allows the navigation of the fourth ventricle, the cerebral aqueduct, and the third ventricle in order to explore the cerebrospinal fluid pathways and eventually aspirate blood clots and surgical debris.METHODSWe report on one patient affected by an ependymoma of the fourth ventricle, for whom we used a flexible neuroendoscope to explore and clear blood clots from the cerebral aqueduct and the third ventricle after the resection of the tumor in the prone position. Blood is aspirated with a syringe using the working channel of the scope as a sucker.RESULTSA large blood clot that was lying on the roof of the third ventricle was aspirated, setting the ventricle completely free. Other clots were aspirated from the right foramen of Monro and from the optic recess.CONCLUSIONWe describe this novel technique, which represents a safe and efficient way to clear the surgical field at the end of posterior fossa surgery in the prone position. The unusual endoscopic visual perspective and instrument maneuvers are easily handled with proper neuroendoscopic training.


2021 ◽  
Author(s):  
R. Chevreau ◽  
H Ghazale ◽  
C Ripoll ◽  
C Chalfouh ◽  
Q Delarue ◽  
...  

AbstractEpendymal cells with stem cell properties reside in the adult spinal cord around the central canal. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, six of them more than 20 fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr. OSMR is the receptor for the inflammatory cytokine oncostatin (OSM) and we studied its regulation and role using neurospheres derived from ependymal cells. We found that OSM induces strong OSMR and p-STAT3 expression together with proliferation reduction and astrocytic differentiation. Conversely, production of oligodendrocyte-lineage OLIG1+ cells was reduced. OSM is specifically expressed by microglial cells and was strongly upregulated after injury. We observed microglial cells apposed to ependymal cells in vivo and co-cultures experiments showed that these cells upregulate OSMR in neurosphere cells. Collectively, these results support the notion that microglial cells and OSMR/OSM pathway regulate ependymal cells in injury. In addition, the generated high throughput data provides a unique molecular resource to study how ependymal cell react to spinal cord lesion.


1999 ◽  
Vol 10 (2) ◽  
pp. 238-244
Author(s):  
ADOLFO GARCÍA-OCAÑA ◽  
SUSAN C. GALBRAITH ◽  
SCOTT K. VAN WHY ◽  
KAI YANG ◽  
LINA GOLOVYAN ◽  
...  

Abstract. Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo, the role of PTHrP in the kidney is unknown. To study the effects of injury on PTHrP expression and its consequences in more detail, the immortalized human proximal tubule cell line HK-2 was used in an in vitro model of ATP depletion to mimic in vivo renal ischemic injury. These cells secrete PTHrP into conditioned medium and express the type I PTH/PTHrP receptor. Treatment of confluent HK-2 cells for 2 h with substrate-free, glucose-free medium containing the mitochondrial inhibitor antimycin A (1 μM) resulted in 75% depletion of cellular ATP. After an additional 2 h in glucose-containing medium, cellular ATP levels recovered to approximately 75% of baseline levels. PTHrP mRNA levels, as measured in RNase protection assays, peaked at 2 h into the recovery period (at four times baseline expression). The increase in PTHrP mRNA expression was correlated with an increase in PTHrP protein content in HK-2 cells at 2 to 6 h into the recovery period. Heat shock protein-70 mRNA expression was not detectable under baseline conditions but likewise peaked at 2 h into the recovery period. Treatment of HK-2 cells during the recovery period after injury with an anti-PTHrP(1-36) antibody (at a dilution of 1:250) resulted in significant reductions in cell number and uptake of [3H]thymidine, compared with nonimmune serum at the same titer. Similar results were observed in uninjured HK-2 cells. It is concluded that this in vitro model of ATP depletion in a human proximal tubule cell line reproduces the pattern of gene expression previously observed in vivo in rat kidney after ischemic injury and that PTHrP plays a mitogenic role in the proliferative response after energy depletion.


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