S100b in spinal cord injury

List of abbreviations

CSF

cerebrospinal fluid

SCI

spinal cord injury

MRI

magnetic resonance imaging

CNS

central nervous system

MS

multiple sclerosis

Introduction

Spinal cord injury (SCI) results in severe social–economic problems, because it is observed mostly among younger adults. The incidence of SCI has been reported at 10.5 cases per 100,000 people ( ). This type of injury occurs in young to middle-aged populations due to road traffic accidents, violence, and contact sports. Unfortunately, only 1% of SCI patients experience injuries that fully resolve. Almost half of cases suffer of severe neurological loss (para/tetraparesis, para/tetraplegia) with or without respiratory disturbances ( ).

Several prognostic factors have been proposed according to the previously published studies. But there is still no consensus on which clinical diagnostic tests could be applied to reliably indicate the sub-clinical neurophysiological changes occurring in the spinal cord during the acute phase, and this affects the prediction of cell death and tissue destruction in SCI. Neurological examination provide a general indication of spinal cord neurological function, but are unreliable, especially during the acute phase (first 24 h) after SCI as a result of spinal shock in many patients ( ). MRI provides an accurate anatomical diagnosis, but it is impossible to distinguish neuronal tissue necrosis from post-traumatic edema. Most of the medical decisions are targeting the stabilization of the patients and preventing further injury, but no definitive treatment for the present state of the CNS trauma exists ( ). In these cases, where the real-time injury is the question in clinical diagnosis and prognosis, serum and CSF biomarker evaluation provides another option. A biomarker must be accurate, sensitive, specific, and provide high predictive value. The most widely used biomarker in such cases is S100b, a protein found in cells of neural crest derivation, which can be measured in the serum after disruption of the blood brain barrier ( ). S100b is implicated in a very broad number of CNS conditions, and as such, it is perhaps one of the strongest candidate markers ( ). In case of a CNS injury, accompanied by a nervous tissue and cellular damage, this structural protein is released from nervous cells and its concentration increase extra-cellularly—including CSF and blood. In these cases, S100b could be a potential biomarker of nervous tissue damage ( ).

S100b characteristics

The S-100 protein family constitutes a sub-group of Ca ^{+ 2} -binding proteins. The term “S-100” was used because this protein was soluble in 100% ammonium sulfate and refers to a mixture of dimeric proteins consisting of two sub-units termed α and β ( ). Three isoforms are known. S100a (αβ) is found in glial cells and melanocytes, S-100b (ββ) is present in high concentrations in glial cells and Schwann cells of the central and peripheral nervous systems as well as in Langerhans cells and cells of the anterior pituitary gland and S-100a0 (αα), which represents 5% of the S-100 protein in the brain (hippocampus, olfactory cells). The last is found outside the nervous system in slow-twitch muscle, heart, and kidney ( ). The genes encoding the majority of human S100 proteins are organized in a cluster within the chromosomal region 1q21, while some genes coding individual S100 proteins are located in other chromosomal regions, including 21q22 where, in particular, the gene for the S100b protein is located ( ).

S100b is primarily an astrocytic protein and it was first detected in CSF at the acute phase of exacerbation of MS ( ). The majority of astrocytic S100b is located within the cytoplasm, 5%–7% is membrane bound. At least 80%–90% of the total S100b pool is found within the brain, the remainder being located in other non-neuronal tissues. S100b is thought to be involved in a number of Ca ^{+ 2} -dependent cellular functions, including protein phosphorylation, enzyme activation, cell proliferation and differentiation, cytoskeletal dynamics, intra-cellular Ca ^{+ 2} homeostasis and protection against oxidative injury ( ). In a low concentration it seems to have a neurotrophic effect, it stimulates the growth of neurons, and it increases their survival during development and also during an injury. Higher concentrations might be toxic and evoke cell death. S100b is metabolized and excreted by the kidneys and has a half-life of about 30 min. S100b is found at low levels in healthy patients and remains chemically stable for several hours after sampling ( ).

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