Due to its lipophilicity, bilirubin, which readily binds to membrane lipids and rapidly crosses the blood-brain barrier (KBB), has a deleterious effect on the brain at high serum concentrations [1, 4]. It is known that the risk and severity of neurotoxicity increase as the blood bilirubin level rises; however, it is unknown at what serum bilirubin level the neurotoxic consequences begin to manifest. APA (2004) reported that infants discharged after 72 hours reduced the incidence of neurotoxicity [12].
According to studies [18, 19], abnormal weight loss is a risk factor for newborn jaundice. Pathological weight loss reflects the infant's feeding problems; the risk of severe hyperbilirubinemia is elevated in infants who are not nursed often and, as a result, do not consume sufficient calories. Salas et al. discovered that pathological weight loss in breastfed newborns nearly quadrupled the probability of non-hemolytic severe hyperbilirubinemia [20]. According to Erdeve et alstudy, .'s weight loss of more than 10 percent was observed in 12,4 percent of hospitalized babies with jaundice, and it was determined to be the second most important risk factor for severe hyperbilirubinemia [18]. In our investigation, however, no statistically significant differences in birth weights of newborns with severe hyperbilirubinemia were detected.
In the 2004 APA guideline, jaundice in the first 24 hours and a history of phototherapy in an older sibling were identified as substantial risk factors for severe hyperbilirubinemia [12]. Independent of other risk factors, the presence of a sibling with jaundice and a sibling with severe hyperbilirubinemia increased the risk of jaundice by 3.1 times and the risk of severe hyperbilirubinemia by 12.5 times in a study of 3301 newborns in the United States. The role of genetic factors in the recurrence of hyperbilirubinemia has been emphasized [21]. In the study, the total bilirubin levels of the unwell infants in the experimental group were significantly higher than those of the infants in the control group. Therefore, each infant in the experimental group received phototherapy according to the suggested protocol.
Understanding the relationship between blood biomarkers and injury-induced brain processes is crucial for advancing our pathophysiology understanding of secondary injury in people. Concerns about peripheral indicators of CNS processes include 1) how blood biomarkers mechanically link to brain injury/repair signaling and 2) the potential extracranial sources, if any, that could confound such markers. Recent evidence suggests that in the acute phase following TBI, brain-derived biomarkers enter the circulation via glympathic clearance, and that disruption of glympathic function may impede the clearance of such molecules into the circulation, thereby making peripheral biomarker detection after injury difficult [22–24].
However, disruption of the blood-brain barrier (BBB) and neuroendocrine dysfunction may affect peripheral biomarker levels following brain injury [25]. Indeed, changes in hormones produced by both the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA)-axis can modulate peripheral immune function, and Merchant-Borna et al. [26] observed that 7 days after SRC, gene transcription profiles in peripheral blood leukocytes reflected regulation of the HPA-axis. In addition, we recently established [25] that peripheral catecholamine release is substantially linked with circulating levels of inflammatory cytokines and chemokines following moderate and severe TBI. The activation of neural afferent and efferent pathways can inhibit cytokine production via cholinergic signaling, a mechanism that has been shown to specifically inhibit the production of TNF-a by macrophages [27].
The mechanical trauma that causes traumatic brain injury may damage parenchymal tissue, resulting in the release and transit of certain molecules into the bloodstream. Nonetheless, the examination of CNS damage indicators in peripheral blood after TBI has resulted in a number of significant contributions. s100B is the most researched biomarker in traumatic brain injury [28]. Numerous investigations have demonstrated immediate blood increases in individuals with all types of injuries [29, 30]. GFAP is the primary intermediate filament protein in astrocytes, and, like s100B, it has been investigated extensively across the spectrum of TBI. It is believed that reactive astrocyte gliosis or astrocyte damage leads to the release of GFAP from the CNS following injury [31]. Indeed, acutely high blood concentrations of the protein have been reported across the severity spectrum of TBI [32] and are associated with poor patient prognosis [33]. GFAP may be superior than s100B as a TBI biomarker due to its increased brain specificity, although this is not conclusive. It outperforms s100B in diagnostic sensitivity and specificity in severe injuries and is unaffected by extracranial damage [30]. In the limited number of studies evaluating GFAP-BDP in TBI patients, positive associations with damage severity, structural abnormalities, and the requirement for neurosurgical intervention have been reported [32]. Neuron specific enolase (NSE) is an enzyme involved in glycolysis that is primarily neuronal. Increased blood concentrations have been seen in patients with mild and severe TBI and have been associated with a poor prognosis [33]. NSE's presence in erythrocytes and vulnerability to post-processing hemolysis and extracranial damage [34] have reduced its utility as a biomarker for traumatic brain injury. In addition, comparable to s100B, acute increases in circulating NSE levels have been observed after physical activity [30, 32]. Mutations in the MAPT gene are known to produce tauopathy and are related with the development of neurodegenerative disorders [35]. The blood proteins GFAP, NSE, and S100 were statistically substantially greater in the experimental group than in the control group, as determined by the research findings. Despite the fact that the GDF5 and MAPt values in the patient group were high, they were not statistically significant. This is due to the number of patients in the experimental group.
Limitations of the present study include the small sample size, and the diagnostic significance of blood parameters in newborns with extremely high hyperbilirubinemia should be assessed in future studies with larger sample sizes. In conclusion, our study revealed a rise in serum NSE and GFAP levels upon admission and on the third day in the extremely high hyperbilirubinemia newborn experimental group. In addition, neonates in the control group had significantly elevated s100B levels on the day of admission, but not on the third day. In addition, our data imply that NSE and GFAP may be a viable, possible biomarker for extremely high hyperbilirubinaemia in newborns that merits further investigation.