ABSTRACT
BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.
Subject(s)
Basilar Artery/physiopathology , Interleukin-6/cerebrospinal fluid , Lipids/cerebrospinal fluid , Neurons/metabolism , Subarachnoid Hemorrhage/cerebrospinal fluid , Vasoconstriction , Vasospasm, Intracranial/cerebrospinal fluid , Animals , Apoptosis , Basilar Artery/diagnostic imaging , Biomarkers/cerebrospinal fluid , Disease Models, Animal , Interleukin-6/biosynthesis , Intracranial Pressure , Neurons/pathology , Phosphatidylcholines/cerebrospinal fluid , Phosphatidylethanolamines/cerebrospinal fluid , Pilot Projects , Rabbits , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/pathology , Subarachnoid Hemorrhage/physiopathology , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/pathology , Vasospasm, Intracranial/physiopathologyABSTRACT
Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction (p = 0.03) and consolidation (p = 0.04), while lysophosphatidylcholine (LPC) increased following induction (p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year (p < 0.001), 2 years (p = 0.001) and 3 years (p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory (p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity.
Subject(s)
Central Nervous System/drug effects , Cognition/drug effects , Methotrexate/therapeutic use , Phospholipids/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Central Nervous System/metabolism , Central Nervous System/physiopathology , Child , Child, Preschool , Chromatography, High Pressure Liquid , Cognition/physiology , Female , Humans , Infusions, Intravenous , Male , Methotrexate/administration & dosage , Multivariate Analysis , Neuropsychological Tests , Outcome Assessment, Health Care , Phosphatidylcholines/cerebrospinal fluid , Phosphatidylethanolamines/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/psychology , Sphingomyelins/cerebrospinal fluid , Time FactorsABSTRACT
The author reports of the achieved results in a quantitative study of general lipids, phospholipids and cerebrosides in the CSF of 37 patients with demyelinating diseases, of 11 patients with vascular brain pathology and 7 with Van Bogart's panencephalitis. The control group consisted of 14 patients without focal lesions of the nervous system, with normal CSF indices. In demyelinating diseases there was a significant increase in the content of kephalines and cerebrosides. In Van Bogart's panencephalitis there was a much higher increase of kephalines, general lipids and phospholipids. In vascular brain disorders there was a moderate increase of all lipids. The possible pathochemical mechanisms of the depicted changes in the content of the lipids in the CSF are discussed.
