At HaemoScan we have a broad experience performing brain biomarker assays. We even have our own uniquely developed assay for BFABP/FABP7 and Neuroketal. Below an overview of our commonly performed assays.
Brain fatty acid binding protein (BFABP) is a 15 kD protein, which is specific for brain tissue. It is released from asterocytes after mechanical damage, ischemia and oxidative brain damage. BFABP is determined by means of ELISA with BFABP specific monoclonal capture antibodies and polyclonal detection antibody.
Neuroketal (gamma-ketoaldehyde, isoketal, neuroprostane)
Neuroketals and neuroprostanes are compounds which are produced by free radical induced peroxidation of docosahexenoic acid (DHA). Docosahexenoic acid is a membrane polyunsaturated fatty acid which is abundantly present in the brain and is especially vulnerable to free radical attack because hydrogen radicals easily remove its double bonds. This peroxidation process occurs via the neuroprostane pathway resulting in Neuroketals. Neuroketals in turn, were shown to rapidly adduct to lysine, forming Neuroketal-protein adducts.
The fact that DHA is prone to free radical attack may make Neuroketals a unique and prominent marker of oxidative injury in the brain. Reactive aldehydes are thought to be key mediators of oxidant injury because of their capacity to covalently modify proteins. Thus, generation of Neuroketals may induce neuronal injury due to their reactivity and could potentially be involved in the formation of protein cross-links, a common feature in neurodegenerative diseases.
S-100 is an acidic calcium-binding protein found in the nervous system of vertebrates. It is a dimer of a and b subunits. S-100ß, which consists of two b subunits, is present in high concentration in glial and Schwann cells. It leaks from the cerebrospinal fluid to blood after cerebral damage and is a sensitive indicator of brain injury and increased permeability of the blood brain barrier. The determination of S-100ß concentrations in serum and plasma is performed with a solid-phase immunoluminometric sandwich assay.
Enolase is a glycolytic enzyme present in the cytoplasm of all cells in higher animals. The molecule is a dimer of a, b and g subunits. These subunits are found in aa, bb, gg, ab and ag iso-enzymes. The g containing types occur mainly in neurons, peripheral nerve cells and neuroectodermal cells and are collectively known as neuron-specific enolase (NSE). NSE, being an enzyme from the cellular cytoplasm is not secreted to the extracellular fluid by intact cells but rather is released on lysis. Therefore, NSE is a specific marker for brain damage by cerebral hypoxia-ischemia (for instance after cardiac arrest, cardiac surgery and resuscitation).
The determination of NSE concentrations in serum is performed with an immuno-luminometric assay based on a solid-phase sandwich ELISA technique.
Serum carnosinase is synthesized in the brain, where it is secreted into cerebrospinal fluid and then into the blood stream. After brain damage, e.g. acute ischemic stroke, serum carnosinase levels are reduced. Serum carnosinase catalyses the hydrolysis of homocarnosine (g-aminobutyryl-L-histidine). The activity is determined by measuring the rate of histidine production. Histidine is quantified by reaction with o-phthaldialdehyde, to form a fluorescent product. Enzymatic activity is expressed as nmol histidine formed per min per ml sample volume, and is a measure of serum carnosinase levels.