For decades, research has been focused on identifying bio markers that can improve the early stroke detection and positively modify the clinical, economic, and management outcomes. An ideal stroke biomarker should have the following characteristics:

• Diagnostic sensitivity and specificity

• The ability to differentiate between hemorrhagic and ischemic stroke

• Early and stable release after an acute event

• Predictable plasma clearance

• Potential to define stroke risk

• The ability to guide therapeutic choices

• The possibility of being quantitatively and rapidly measured using cost-effective techniques

The difficulties in identifying a biomarker to introduce in clinical practice are mainly related to the slow release of glial and neuronal proteins across the blood–brain barrier after stroke or traumatic injury and the reduced diagnostic specificity (they increase in many clinical situations simulating stroke).

Following cerebral ischemia, there is an increased pro duction of oxygen free radicals, which triggers the inflammatory response activation that results in the recruitment into the damaged brain tissue of various immune cells, such as macrophages, neutrophils, and T lymphocytes. These inflammatory cells release proinflammatory cytokines, such as interleukin-6 (IL-6), which can cross the blood–brain barrier and reach circulation. In addition, biomarkers such as D-dimer and those that play a role in platelet function are involved in thrombus formation and propagation. The heart and large-caliber vessels, such as the aorta, are among the main sites of thrombus formation; the inability of the cardiovascular system to release sufficient blood to the brain may worsen the stroke outcome.

Several biomarkers have been identified in the various stages of stroke pathogenesis (oxidative damage, inflammation, thrombus formation, cardiac function, and brain dam age) (Table 1).

Table1. Biomarkers of stroke according to the pathogenesis

Other biomarkers currently under investigation are:

 • Lipoprotein-associated phospholipase A2 (Lp-PLA2)

 • Asymmetrical dimethylarginine (ADMA)

• Matrix metalloproteinase-9 (MMP-9)

• S100-β protein

• N-methyl-D-aspartic acid (NMDA) receptor peptides and their antibodies

• Glial fibrillary acidic protein (GFAP)

• Parkinson disease protein 7 (PARK-7)

• Nucleotide diphosphate kinase A (NDKA)

Lp-PLA2

 Lp-PLA2 is a calcium-dependent serine lipase that hydrolyzes oxidized phospholipids to release proinflammatory lysophosphatidylcholine and oxidized fatty acids. It circulates bound mainly to low-density lipoprotein (LDL) and partly to small, dense high-density lipoprotein (HDL) (anti- atherogenic effect). Lp-PLA2 is produced and expressed in macrophage-rich atherosclerotic lesions and represents an independent inflammatory marker of cardiovascular risk and a predictor of ischemic stroke.

ADMA

The post-translational methylation of L-arginine produces the ADMA molecule. After proteolysis, it is released as free dimethylarginine along with symmetric (inactive) dimethyl arginine. It is a potent nitric oxide synthase (NOS) inhibitor. Its levels are detectable in the blood, urine, and cerebrospinal fluid; the plasma form has been proposed as a predictive marker of stroke risk.

MMP-9

MMP-9 belongs to the family of zinc- and calcium- dependent endopeptidases responsible for the turnover and degradation of extracellular matrix proteins. It plays an essential role in several processes, including tissue remodeling, phlogosis, angiogenesis, and metastasis. In the brain, its expression is physiologically very low or undetectable, while its levels increase significantly early in the ischemic brain; in the acute phase, its concentrations correlate with the extent of ischemia, poor prognosis, and complications from hemorrhagic transformation. Several studies have highlighted the role of MMP-9 in stroke pathogenesis, including loss of blood–brain barrier integrity, neuronal death, and hemorrhage following stroke. In addition, MMP-9 plays a reparative role during brain regeneration and neurovascular remodeling in the subsequent phase of tissue repair.

S100-β

S100-β is a glial protein consisting of α- and β-subunits that combine in hetero- and homodimers (α–α, α–β, β–β); S100-β includes the β–β and α–β forms. It is present in melanocytes, adipocytes, and chondrocytes but is highly specific for the nerve tissue, localized in the cerebral astro glial compartment, and Schwann cells, which line peripheral nerve fibers. S100-β represents a not specific biomarker of blood–brain barrier dysfunction with a concentration in the cerebrospinal fluid significantly higher than in the serum (40:1). It has emerged as a biomarker of early ischemic stroke with a peak after 24 h. It correlates well with the extent of the infarct area. In addition, it allows differential diagnosis between ischemic and hemorrhagic stroke or stroke-mimicking diseases. One of the main disadvantages is its poor specificity, as it increases during other neurological pathologies.

NMDA Receptor Peptides

NMDA receptor peptides bind glutamate and are present on neurons throughout the encephalon. They consist of four subunits, 2 NR1 and 2 NR2. During ischemia, fragmentation of NR2 into NR2A and NR2B and production of anti NR2 antibodies are observed. Therefore, NR2 fragments and their antibodies represent markers of ischemic stroke and TIA.

GFAP

GFAP is a monomeric filamentous protein specific to brain astrocytes. Its levels increase during ischemic stroke, peaking 2–4 days after the onset of symptoms. It also allows differential diagnosis between ischemic and hemorrhagic stroke.

PARK7

PARK7 has a reparative role in neurological damage in oxidative stress processes; its levels increase during stroke, with a peak between 30 min and 3 h after the symptoms onset. It does not allow making a differential diagnosis between ischemic and hemorrhagic stroke or TIA.

NDKA

NDKA is an enzymatic protein of neurons whose levels increase during stroke, with a peak between 30 min and 3 h after the symptoms onset. It does not allow the differential diagnosis between ischemic and hemorrhagic stroke, or TIA.

Table 2 shows the potential clinical applications of biomarkers at various stages of the disease, from risk prediction to diagnosis, differential diagnosis, and prognosis.

Table2. Potential clinical application of stroke biomarkers

Given the high heterogeneity of stroke, a single biomarker may not be sufficient to capture the different aspects of stroke pathogenesis. Therefore, a multi-marker strategy that assesses the various stroke-related molecular alterations may be necessary. Translating stroke biomarkers into clinical practice is a goal of many researchers, clinicians, and pharmaceutical industries.

اخر الاخبار

اخبار العتبة العباسية المقدسة

جمعية العميد تستعدّ لإطلاق النسخة الثانية من الملتقى العلمي الوطني للنخب الشبابية

مكتب المتولي الشرعي للشؤون النسوية ينظّم ورشة تدريبية في كتابة الخبر الصحفي

قسم الشؤون الفكرية يقيم ندوة ثقافية لعدد من صناع المحتوى الهادف في ذي قار

العتبة العباسية المقدسة: أجنحة معرض الكتاب لمهرجان رحمة للعالمين ستشهد مشاركة العتبات المقدسة والمراكز الفكرية

المزيد

الآخبار الصحية

تحذير من الإفراط في شربها.. متى تصبح الماتشا خطيرة؟

من بناء العضلات إلى "تسميم الجسم".. الوجه الآخر للبروتين ؟

دراسة جديدة: مخ الانسان يغتسل أثناء النوم

هل من الآمن شرب القهوة على معدة فارغة؟

المزيد

الآخبار التكنلوجية

مزايا مرآة الرؤية الخلفية ذاتية التعتيم في السيارات

دراسة.. كوكب غريب أمد الأرض بمقومات الحياة !

يهدد عرش هوليود.. أول فيلم رسوم متحركة بالذكاء الاصطناعي

أكبر تغيير منذ سنوات.. هل تكشف أبل النقاب عن "iPhone Air"؟

المزيد

مواضيع ذات صلة

Soluble IL-33 Receptor (sST2)

syphilis detection test (Serologic test for syphilis [STS], Venereal Disease Research Laboratory [VDRL], Rapid plasma reagin [RPR], Fluorescent treponemal antibody test [FTA])

sweat test (Sweat electrolyte test, Sweat chloride test, Sweat conductivity test, Iontophoretic sweat test)

substance abuse testing (Urine drug testing, Drug testing, Drug screening, Toxicology screening)

Streptococcus serologic testing (Antistreptolysin O titer [ASO], Antideoxyribonuclease-B titer, [Anti-DNase-B, ADNase-B, ADB], Streptococcus group B antigen detection, Streptozyme)

Galectin-3

Biomarkers of Collagen Synthesis and Degradation

Cardiac Fibrosis

stool for leukocytes (White blood cell stool test, Fecal leukocyte stain, Stool for white cells)

stool culture (Stool for culture and sensitivity [C&S], Stool for ova and parasites [O&P])

stool cancer screening (stool for occult blood, Stool for OB, Fecal occult blood test [FOBT], Fecal immunotest [FIT], DNA stool sample)

Biomarkers of Myocardial Remodeling and Fibrosis