The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir–treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.

Ischemic stroke is a serious medical event that cannot be predicted in advance and can have long-lasting effects on patients, families, and communities. A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue. In recent years, research into regulatory long non-coding (lnc)RNAs, a diverse group of RNA molecules with regulatory functions, has emerged as a promising direction in the study of cerebral infarction. This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction, as well as potential strategies for their application in clinical settings. LncRNAs have the potential to act as “sponges” that attract specific microRNAs, thereby regulating the expression of microRNA target genes. These interactions influence various aspects of ischemic stroke, including reperfusion-induced damage, cell death, immune responses, autophagy, angiogenesis, and the generation of reactive oxygen species. We highlight several regulatory lncRNAs that have been utilized in animal model treatments, including lncRNA NKILA, lncRNA Meg8, and lncRNA H19. Additionally, we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction, such as lncRNA FOXO3, lncRNA XIST, and lncRNA RMST. The lncRNAs hold potential for genetic-level treatments in patients. However, numerous challenges, including inefficiency, low targeting accuracy, and side effects observed in preliminary studies, indicate the need for thorough investigation. The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.

Vascular dementia is a highly heterogeneous neurodegenerative disorder induced by a variety of factors. Currently, there are no definitive treatments for the cognitive dysfunction associated with vascular dementia. However, early detection and preventive measures have proven effective in reducing the risk of onset and improving patient prognosis. Nitric oxide plays an integral role in various physiological and pathological processes within the central nervous system. In recent years, nitric oxide has been implicated in the regulation of synaptic plasticity and has emerged as a crucial factor in the pathophysiology of vascular dementia. At different stages of vascular dementia, nitric oxide levels and bioavailability undergo dynamic alterations, with a marked reduction in the later stages, which significantly contributes to the cognitive deficits associated with the disease. This review provides a comprehensive review of the emerging role of nitric oxide in the physiological and pathological processes underlying vascular dementia, focusing on its effects on synaptic dysfunction, neuroinflammation, oxidative stress, and blood‒brain barrier integrity. Furthermore, we suggest that targeting the nitric oxide soluble guanylate cyclase-cyclic guanosine monophosphate pathway through specific therapeutic strategies may offer a novel approach for treating vascular dementia, potentially improving both cognitive function and patient prognosis. The review contributes to a better understanding of the multifaceted role of nitric oxide in vascular dementia and to offering insights into future therapeutic interventions.

There is a significant global death and disability rate associated with ischemic stroke, making it one of the most prevalent disorders. With the increasing worldwide aging population, the prevalence of ischemic stroke has notably increased and has emerged as a pivotal issue in public health. The neurovascular unit primarily consists of neurons, astrocytes, microglia, and brain microvascular endothelial cells. These cells are structurally tightly connected; together, they maintain the balance of brain function and are crucial for brain function and cerebral ischemic damage. Emerging studies in recent years have demonstrated the development of associations between ischemic stroke and the vascular neural units. The neurovascular unit characterizes the whole-tissue response to stroke, encompassing the interrelationship and reciprocal impact of neurons, glial cells, and microvessels. The neurovascular unit results in compromised integrity of the microvasculature and blood–brain barrier, neuronal cell death, the glial response, the inflammatory response, and immune cell infiltration, all of which are strongly associated with the course of ischemic stroke. This narrative review explores the complex relationship between ischemic stroke and the neurovascular unit in the context of an aging population. With aging, the neurovascular unit undergoes structural and functional changes that predispose the elderly to higher risks of stroke and complicate recovery post-stroke. We explore the impact of aging on the neurovascular unit, focusing on how age-related alterations in the neurovascular unit contribute to the susceptibility to ischemic stroke and influence the repair mechanisms post-stroke. The review highlights the compromised integrity of the microvascular and blood-brain barriers, increased neuronal cell death, heightened glial response, inflammatory reactions, and immune cell infiltration associated with aging, all of which are critical in the progression of ischemic stroke. By examining the latest research, we aim to provide a comprehensive understanding of the neurovascular unit’s role in ischemic stroke within the aging population and discuss how regenerative medicine offers novel strategies for treatment, emphasizing neuroprotection, neuroregeneration, and neurorepair. These aspects are of paramount importance for clinical interventions tailored to the elderly, who often present with unique challenges in stroke management. The review underscores the importance of considering the aging factor in stroke research and treatment, as the cellular interactions within the neurovascular unit form a complex system that is significantly influenced by the aging process. These connections cannot be overlooked in the quest for effective stroke therapies. The development of regenerative medicine presents new perspectives on stroke treatment, particularly for the elderly, where traditional therapies may be less effective or carry higher risks. This narrative review aims to bridge the gap in knowledge regarding the neurovascular unit’s role in ischemic stroke within the context of aging, providing a foundation for the development of targeted therapies that can improve outcomes for this vulnerable population.

Ischemic stroke is a leading cause of disability and mortality worldwide. Recently, increasing evidence implicates microRNAs (miRs) in the pathophysiology of ischemic stroke. Studies have shown that miR-15a/16-1 is abnormally expressed in brains after ischemic stroke, and its upregulation may increase ischemic damage. Given that sex and age are significant modifiers of stroke outcomes, here we investigated whether inhibiting miR-15a/16-1 with antagomirs mitigates cerebral ischemia/reperfusion (I/R) injury in a sex- and age-dependent manner. Young (3 months) and aged (18 months) male and female C57/BL mice underwent 1-h middle cerebral artery occlusion and 3–7 days reperfusion (tMCAO). We administered miR-15a/16-1 antagomir (30 pmol/g) or control antagomir (NC, 30 pmol/g) via tail vein 2 h post-MCAO. Neurobehavioral testing and infarct volume assessment were performed on days 3 and 7. Compared to controls, antagomir treatment significantly improved neurobehavioral outcomes and reduced infarct volume in tMCAO mice at day 7, with the effects being more pronounced in young mice. Notably, young female mice exhibited superior survival and sensorimotor function compared to young male mice. These results were also replicated in a permanent MCAO (pMCAO) mice model. This suggests miR-15a/16-1 antagomir and estradiol may synergistically regulate genes involved in neurovascular cell death, inflammation, and oxidative stress, with sex and age-dependent expression of miR-15a/16-1 and its targets likely underlying the observed variations. Overall, our findings identify miR-15a/16-1 antagomir as a promising therapeutic for ischemic stroke and suggest that sex and age should be considered when developing miR-based therapeutic strategies.

Traumatic brain injury (TBI) is a prevalent disease that poses a significant threat to global public health. Digestive dysfunction, as a common complication, is of particular importance to understand its pathogenesis, diagnostic criteria, and relevant treatment strategies. TBI can affect digestive function through inflammatory immune responses, the enteric nervous system, and hormonal levels. Furthermore, TBI can also impact neurologic recovery through bidirectional communication along the brain-gut axis. Therefore, this article aims to summarize the underlying mechanisms and further explore individualized feeding strategies, therapeutic approaches, long-term prognosis for TBI patients, as well as recent advancements in related technologies. Further understanding of the pathogenesis of digestive system dysfunction after TBI on the basis of the interaction of gut-brain axis is conducive to more future therapies to treat TBI and improve the long-term prognosis of patients through improving digestive function, and achieve good clinical efficacy.