Abstract

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. 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 h 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. 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. Altered levels of Aβ peptides, NF-L and tau may reflect brain tissue injury following ICH surgery. However, the dynamics of biomarker levels in the different fluid compartments should be considered in the study of pathophysiology or biomarkers in ICH patients.

Highlights

  • Spontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke

  • Biomarkers in extracellular fluid (ECF) such as amyloid-beta peptides (Aβ) and tau have been sampled by MD in patients suffering from subarachnoid hemorrhage (SAH)[7,8,9,10] and traumatic brain injury (TBI)[9,11,12,13,14,15,16], no previous studies exist in ICH ­patients[16]

  • The dynamics were different in the three compartments without any correlations across ECF, cerebrospinal fluid (CSF) and plasma, emphasising that for adequate interpretation of cerebral events leading to the release of a biomarker, knowledge of the relationship of biomarker levels in different compartments is crucial

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Summary

Introduction

Spontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke. To refine treatments, improved understanding of the secondary injury processes is needed. 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. Biomarkers in ECF such as amyloid-beta peptides (Aβ) and tau have been sampled by MD in patients suffering from subarachnoid hemorrhage (SAH)[7,8,9,10] and traumatic brain injury (TBI)[9,11,12,13,14,15,16], no previous studies exist in ICH ­patients[16]. We aimed to compare levels of biomarkers in three compartments; ECF, CSF and plasma at three time points during the initial 60 h following ICH surgery. We hypothesised that the levels of Aβ, tau and NF-L, monitored by MD, would be different in the vicinity of the ICH (the perihemorrhagic zone; PHZ), when compared to those in the non-injured cortex (NCX)

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