Intracranial hemorrhage (ICH) is defined as any type of intracranial hemorrhage that kills neurons and pressures surrounding brain tissue, causing neurological impairments (1, 2). ICH accounts for 10–20% of all strokes and is the second most common subtype of stroke, with significant impairment or death as a result (3, 4). The prevalence of ICH varies greatly between countries and ethnic groups, with ICH in low- and middle-income countries being twice as common as in high-income countries (5). The incidence of ICH is 8–15% in Western countries such as the United States, United Kingdom and Australia, 18–24% in Japan and South Korea, and 14.9% in China (6–8). The average cost of initial hospitalization for ICH survivors was $28,360 and the first year after discharge was $16,035, with 8% requiring repeat hospitalizations and 41% unable to take care of themselves (9). The high morbidity, high cost, and disability rate of ICH make it an important factor restricting social and economic development, and the search for the potential etiology and biological targets of ICH has become an urgent need.

The globin isoform neuroglobin is found in both the central and peripheral neural systems (10). Thorsten Burmester et al. were the first to find it in 2000 (11). Its primary role is in maintaining cellular oxygen homeostasis and scavenging reactive oxygen species and nitrogen. It also improves brain tissue's oxygen supply capacity and protects it from hypoxic or ischemia damage, potentially lowering ischemic hypoxic brain injury (12, 13).

Cognitive impairment appears to be a common sequelae of (ICH) survivors, but effective prevention and treatment methods are still lacking (14, 15). Neuroglobin, as a potential neuroprotective protein discovered in recent years, is endowed with relatively broad application prospects (16). The goal of our research was to see if neuroglobin may be used as a biomarker for cognitive impairment following ICH.

We investigated the value of serum neuroglobin in predicting cognitive impairment after ICH. Our study found that serum neuroglobin concentrations were significantly lower in PSCI patients than in non-PSCI patients after ICH. Correlation regression analysis found that serum neuroglobin was an independent predictor of PSCI after ICH. Our further ROC analysis found that neuroglobin has high sensitivity and specificity in predicting PSCI after ICH, suggesting that it has a high value as a predictor of PSCI after ICH.

Neuroglobin is a monomeric hexametric heme protein with a molecular weight of 17 kda, belonging to the globin family, which is mainly expressed in neurons of the central and peripheral nervous systems (19, 20). Neuroglobin is a heme protein that is highly conserved during evolution, with more than 90% genetic sequence identity between humans and mice (21, 22). Neuroglobin is widely distributed in the human body, including the hippocampus, diencephalon, cerebral cortex, cerebellum, organs with endocrine functions, and retinal cells (23). Neuroglobin has a common 8 α-helix structure, and its main physiological function is to bind and transport oxygen, scavenge and detoxify reactive oxygen species (24). The heme prosthetic group of neuroglobin that transports oxygen is located between the fifth and sixth helices. Neuroglobin is mainly expressed intracellularly, and it cannot pass through normal cell membranes and blood-brain barrier, which limits its application (25–27).

Neuroglobin has been found to have neuroprotective effects in recent years. The research of Professor Jin Kunlin's team showed that the neuroglobin level in the autopsy brain tissue of Alzheimer's disease patients increased compared with the normal control group (28). Italian scholars have found that the causative gene of Huntington's disease can damage the 17β-estradiol/neuroglobin signaling pathway, thereby affecting neuronal survival, suggesting that neuroglobin is involved in the pathogenic mechanism of Huntington's disease (29). In addition, the expression of neuroglobin present in the substantia nigra and striatum was upregulated in a mouse model of Parkinson's disease, suggesting that neuroglobin may be involved in the mechanism of its pathogenesis (30, 31). The above studies suggest that neuroglobin has a neuroprotective role in neurodegeneration. Another study showed that neuroglobin could be detected in multiple regions after cerebral infarction, and its expression was significantly increased in the ischemic penumbra (32). Based on the neuroprotective effect of neuroglobin, scientists developed a hyaluronic acid nanoparticle delivery system that can pass through the BBB (33), breaking through the application dilemma of neuroglobin to a certain extent.

The role of neuroglobin in hemorrhagic stroke has also received increasing attention. Cai et al.'s study showed that serum neuroglobin concentration on the second day after subarachnoid hemorrhage was closely related to poor prognosis, suggesting that it may be a potential biological target for predicting poor prognosis of subarachnoid hemorrhage (34). Another study showed that neuroglobin expression was significantly increased in the surrounding neurons of arteriovenous malformation and ICH patients and in the perihematoma area near cerebral hemorrhage, which may be involved in neuroprotection after brain injury (35). A recent study showed that early serum neuroglobin concentration predicts delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage (36). However, the role of neuroglobin in ICH remains poorly understood.

Our study is the first to demonstrate that serum neuroglobin is associated with PSCI after ICH. However, our study also has some limitations. First, we are a single-center study and include no normal controls; second, our main research object is the northern Han population in China, and the findings may not be applicable to other regions and ethnic groups; third, there is a lack of in vitro and in vivo studies on the neuroprotective mechanism of neuroglobin.

Serum neuroglobin concentration may be a potential biomarker for predicting PSCI after ICH. The correlation between serum neuroglobin and PSCI after ICH needs to be further studied, and the research results may provide new prospects for the prevention and treatment of PSCI after ICH.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of Jinzhou Medical University. The patients/participants provided their written informed consent to participate in this study.

YH designed this research and wrote the manuscript. YG, BW, and YM participated in experimental process and statistical analysis. All authors approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.