Characterization of metabolomics profile changes during development of post-traumatic epilepsy in Rat Cerebrospinal Fluid (part-II)
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus Norvegicus
TISSUE(S): Cerebrospinal Fluid
DISEASE(S): Epilepsy
PROVIDER: ST001021 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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| ST001020 | MetabolomicsWorkbench
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| ST001022 | MetabolomicsWorkbench
Project description:BackgroundSyringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.MethodsA rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 μL quisqualic acid (QA) and an injection of 5 μL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC-MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords.ResultsWe demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine.ConclusionsIn summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.
| S-EPMC10895764 | biostudies-literature
Project description:The vascularized nasoseptal flap has become a principal reconstructive technique for the closure of endonasal skull base surgery defects. Despite its potential utility, there has been no report describing the use of the modern nasoseptal flap to repair traumatic cerebrospinal fluid (CSF) leaks and documenting the outcomes of this application. Specific concerns in skull base trauma include septal trauma with disruption of the flap pedicle, multiple leak sites, and issues surrounding persistent leaks after traumatic craniotomy. We performed a retrospective case series review of 14 patients who underwent nasoseptal flap closure of traumatic CSF leaks in a tertiary academic hospital. Main outcome measures include analysis of clinical outcome data. Defect etiology was motor vehicle collision in eight patients (57%), prior sinus surgery in four (29%), and assault in two (14%). At the time of nasoseptal flap repair, four patients had failed prior avascular grafts and two had previously undergone craniotomies for repair. Follow-up data were available for all patients (mean, 10 months). The overall success rate was 100% (no leaks), with 100% defect coverage. The nasoseptal flap is a versatile and reliable local reconstructive technique for ventral base traumatic defects, with a 100% CSF leak repair rate in this series.
| S-EPMC3312593 | biostudies-other
Project description:This study aimed to identify specific CSF miRNAs for diagnosing and monitoring leptomeningeal metastasis with lung adenocarcinoma. In discovery phase, we performed miRNA microarray analysis in matched CSF samples from leptomeningeal metastasis patients at diagnosis and after initial leptomeningeal metastasis-directed therapy.
2020-02-26 | GSE125192 | GEO
Project description:BackgroundIntraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH.MethodsCSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey's post-test ANOVA analysis were used for pair-wise comparisons.ResultsCSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 - < 0.0001), LGIVH (p = 0.023 - < 0.0001), and HGIVH (p = 0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 - 0.0008) in the whole cohort.ConclusionsCSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.
| S-EPMC8710025 | biostudies-literature
Project description:Recently, there have been emerging interests in the area of microvesicles and exosome (MV/E) released from brain cells in relation to neurodegenerative diseases. However, only limited studies focused on MV/E released post-traumatic brain injury (TBI) as they highlight on the mechanistic roles of released proteins. This study sought to examine if CSF samples from severe TBI patients contain MV/E with unique protein contents. First, nanoparticle tracking analysis determined MV/E from TBI have a mode of 74-98 nm in diameter, while control CSF MV/E have a mode of 99-104 nm. Also, there are more MV/E were isolated from TBI CSF (27.8-33.6 × 108/mL) than from control CSF (13.1-18.5 × 108/mL). Transmission electron microscopy (TEM) visualization also confirmed characteristic MV/E morphology. Using targeted immunoblotting approach, we observed the presence of several known TBI biomarkers such as αII-spectrin breakdown products (BDPs), GFAP, and its BDPs and UCH-L1 in higher concentrations in MV/E from TBI CSF than their counterparts from control CSF. Furthermore, we found presynaptic terminal protein synaptophysin and known exosome marker Alix enriched in MV/E from human TBI CSF. In parallel, we conducted nRPLC-tandem mass spectrometry-based proteomic analysis of two control and two TBI CSF samples. Ninety-one proteins were identified with high confidence in MV/E from control CSF, whereas 466 proteins were identified in the counterpart from TBI CSF. MV/E isolated from human CSF contain cytoskeletal proteins, neurite-outgrowth related proteins, and synaptic proteins, extracellular matrix proteins, and complement protein C1q subcomponent subunit B. Taken together, following severe TBI, the injured human brain released increased number of extracellular microvesicles/exosomes (MV/E) into CSF. These TBI MV/E contain several known TBI biomarkers and previously undescribed brain protein markers. It is also possible that such TBI-specific MV/E might contain cell to cell communication factors related to both cell death signaling a well as neurodegeneration pathways.
| S-EPMC6359938 | biostudies-literature
Project description:BackgroundCharcot spinal arthropathy, also known as Charcot spine and neuropathic spinal arthropathy, is a progressive and destructive condition that affects an intervertebral disc and the adjacent vertebral bodies following loss of spinal joint innervation. We report the first case of Charcot spinal arthropathy (CSA) associated with cerebrospinal fluid (CSF)-cutaneous fistula.Case presentationA 54-year-old male who underwent T10-L2 posterior instrumented spinal fusion seven years prior for treatment of T11 burst fracture and accompanying T11 complete paraplegia visited our department complaining of leakage of clear fluid at his lower back. The patient had also undergone various types of skin graft and myocutaneous flap surgeries for treatment of repetitive pressure sores around his lumbosacral area. The patient presented with persistent CSF leakage from a cutaneous fistula (CSF-cutaneous fistula) formed in a lumbosacral pressure sore. The CSF-cutaneous fistula arose from the L5 post-traumatic CSA. Surgery was planned for management of CSF-cutaneous fistula and post-traumatic L5 CSA. We successfully treated the CSF-cutaneous fistula with ligation and transection of the dural sac and cauda equina at the L2-L3 level. In addition, the post-traumatic L5 CSA was successfully treated with a posterior four-rod spinopelvic fixation from T9 to ilium and S2 foramina. After surgery, the CSF leakage stopped and no other adverse neurological changes were found. The four-rod spinopelvic construct was well maintained five years later.ConclusionsCSA associated with CSF-cutaneous fistula is a very rare disorder. Only surgical treatment for both CSA and CSF-cutaneous fistula with ligation and transection of the dural sac and posterior four-rod spinopelvic fixation can bring satisfactory results.
| S-EPMC7325221 | biostudies-literature
Project description:Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K+ transporters, particularly the Na+, K+, Cl-, and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K+ clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K+ clearance through the ChP in the critical period during postnatal neurodevelopment in mice.
| S-EPMC7815709 | biostudies-literature