Extracellular Fluid, Cerebrospinal Fluid and Plasma Biomarkers of Axonal and Neuronal Injury Following Intracerebral Hemorrhage

Abstract

Background: Spontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke. To refine treatments, improved understanding of the secondary injury processes is needed. We compared energy metabolic, amyloid and neuroaxonal injury biomarkers in extracellular fluid (ECF) from the perihemorrhagic zone (PHZ) and non-injured (NCX) brain tissue, cerebrospinal fluid (CSF) and plasma. Method: Patients (n=11, age 61 ± 10 years) undergoing ICH surgery received two microdialysis (MD) catheters, one in PHZ, and one in NCX. ECF was analysed at three time intervals within the first 60 hours post- surgery, as were CSF and plasma samples. Amyloid-beta (Aβ) 40 and 42, microtubule associated protein tau (tau), and neurofilament-light (NF-L) were analysed using Single molecule array (Simoa) technology.Results: Median biomarker concentrations were lowest in plasma, higher in ECF and highest in CSF. Biomarker levels varied over time, with different dynamics in the three fluid compartments. In the PHZ, ECF levels of Aβ40 were lower, and tau higher when compared to the NCX.Conclusion: Altered levels of Aβ peptides, NF-L and tau may reflect brain tissue injury following ICH surgery. However, the different biomarker levels, and their dynamics, in the different fluid compartments should be considered when used to monitor ICH patients.

Extracellular vimentin is sufficient to promote cell attachment, spreading, and motility by a mechanism involving N-acetyl glucosamine-containing structures

“…Potent mechanisms have developed to depolymerize and clear large cytoskeletal filaments such as F-actin from the bloodstream where they otherwise have damaging or pro-inflammatory effects on vasculature and other organs (1-3). Perhaps because of the chemical instability of microtubules in GTP-devoid extracellular fluids no such scavenging system has been described for tubulin, although release of microtubule-binding proteins such as tau is associated with neurodegenerative disease (4)(5)(6)(7). Intermediate filaments (IFs), the most stable element of the cytoskeleton, also do not appear to have active extracellular clearance mechanisms, and studies implicate extracellular IF proteins, especially extracellular vimentin, in a range of human diseases (8)(9)(10)(11)(12).…”

A minimally-invasive method for serial cerebrospinal fluid collection and injection in rodents with high survival rates

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Cerebrospinal fluid (CSF) is a clear fluid surrounding and nourishing the brain and spinal cord.Molecular profiling of the CSF is a common diagnostic approach for central nervous system (CNS) diseases, including infectious diseases, autoimmune disorders, brain hemorrhage and traumatic brain injury, CNS tumors, and Alzheimer's disease [1][2][3][4][5][6][7][8][9][10] . Rodent models are critical for investigating CNS disease mechanisms and therapeutics, however, both collecting CSF and injecting materials into CSF in small animals are technically challenging and often result in high rates of postoperative mortality.

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