Neuron-Specific Enolase-What Are We Measuring?

Since the discovery of the neuron-specific protein by Moore and McGregor in 1965, tens of thousands of studies have investigated the basic and applied significance of neuron-specific enolase (NSE). This promising biomarker, according to many researchers, has not found widespread use in clinical practice, particularly in acute cerebrovascular accidents. Moreover, the several studies refuting the usefulness of serum NSE measurement in critically ill patients leads us to consider the reasons for such contradictory conclusions. In this article, we have analyzed the main directions in the study of NSE and expressed our perspective on the reasons for the contradictory results and the difficulties in implementing the results of these studies in clinical practice. In our opinion, the method of the enzyme-linked immunosorbent assay (ELISA) used in the majority of the studies is inappropriate for the evaluation of NSE as a marker of central nervous system damage, because it does not allow for the differentiation of heterodimers of enolases and the assessment of the enzymatic activity of this group of enzymatic proteins. Therefore, the methodological approach for the evaluation of NSE (γγ-enolase) as a biomarker needs to be elaborated and improved. Furthermore, the specificity of the applied research methods and the appropriateness of the continued use of the term "neuron-specific enolase" must be addressed.

Neuroprotective Effects of Krypton Inhalation on Photothrombotic Ischemic Stroke.

This is the first in vivo study to investigate the neuroprotective effects of krypton on focal cerebral ischemia. The aim of the study was to analyze the effect of 2 h of inhalation of a krypton-oxygen mixture (Kr 70%/O2 30%) on the recovery of neurological functions and the degree of brain damage in rats after photoinduced ischemic stroke (PIS) and to investigate the possible mechanisms responsible for this neuroprotection. Experiments were performed on male Wistar rats weighing 250-300 g (n = 32). Animals were randomized into four groups. Two groups (n = 20) underwent photoinduced ischemic stroke, followed by 2 h of inhalation of krypton-oxygen mixture consisting of Kr 70%/O2 30% or a nitrogen-oxygen breathing mixture consisting of N2 70%/O2 30%, followed by neurological examinations on days 3 and 7. The other two groups (n = 12) received only gas mixtures of the same concentration and exposure duration as in those in the PIS groups, then Western blot analysis of the potential molecular mechanisms was performed. The results of the study show that treatment with the krypton-oxygen mixture consisting of Kr 70%/O2 30% improves the neurological status on day 7 of observation, reduces the lesion volume according to the MRI examination and the number of Iba-1- and caspase-3-positive cells in the damaged area, promotes the activation of neoangiogenesis (an increase in the von Willebrand factor), and reduces the penumbra area and the number of NeuN-positive cells in it on day 14 of observation. Inhalation of the krypton-oxygen mixture also significantly increases the levels of phosphorylated AKT kinase (protein kinase B) and glycogen synthase kinase 3b (pGSK3b) and promotes the expression of transcription factor Nrf2, which was accompanied by the lowered expression of transcription factor NFkB (p50). Thus, we showed pronounced neuroprotection induced by krypton inhalation after stroke and identified the signaling pathways that may be responsible for restoring neurological functions and reducing damage.