Presumed etiology of preterm birth: brain injury and neurodevelopmental outcomes
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Positive impact of sodium L-lactate supplementation on blood acid-base status in preterm newborns
Preclinical studies indicate that lactate is a crucial cerebral energy substrate, with Na-L-lactate administration significantly reducing brain lesion volumes and improving motor and cognitive functions following neonatal hypoxia-ischemia in rat pups. Its neuroprotective effects are linked to neuronal metabolic utilization, making it a promising candidate for treating newborns with hypoxia-ischemia encephalopathy, a condition where hypothermia remains the only established therapy. However, before initiating a clinical trial, it is necessary to assess the effects of Na-L-lactate infusion on blood parameters.
Different types of cell death and their interactions in myocardial ischemia–reperfusion injury
Myocardial ischemia–reperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow is restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, is pivotal in myocardial I/R injury. Preventing cell death during the process of I/R is vital for improving ischemic cardiomyopathy. These multiple forms of cell death can occur simultaneously, interact with each other, and contribute to the complexity of myocardial I/R injury. In this review, we aim to provide a comprehensive summary of the key molecular mechanisms and regulatory patterns involved in these five types of cell death in myocardial I/R injury. We will also discuss the crosstalk and intricate interactions among these mechanisms, highlighting the interplay between different types of cell death. Furthermore, we will explore specific molecules or targets that participate in different cell death pathways and elucidate their mechanisms of action. It is important to note that manipulating the molecules or targets involved in distinct cell death processes may have a significant impact on reducing myocardial I/R injury. By enhancing researchers’ understanding of the mechanisms and interactions among different types of cell death in myocardial I/R injury, this review aims to pave the way for the development of novel interventions for cardio-protection in patients affected by myocardial I/R injury.
Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration
Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.
Nasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent Treg–microglia crosstalk
Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (Treg cells) that migrated to the brain and closely contacted microglia. Treg cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo abrogated the beneficial effects of nasal anti-CD3. However, the adoptive transfer of IL-10-producing Treg cells to TBI-injured mice restored these beneficial effects by enhancing microglial phagocytic capacity and reducing microglia-induced neuroinflammation. These findings suggest that nasal anti-CD3 represents a promising new therapeutic approach for treating TBI and potentially other forms of acute brain injury.
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
In the context of global ageing, the prevalence of neurodegenerative diseases and dementia, such as Alzheimer’s disease (AD), is increasing. However, the current symptomatic and disease-modifying therapies have achieved limited benefits for neurodegenerative diseases in clinical settings. Halting the progress of neurodegeneration and cognitive decline or even improving impaired cognition and function are the clinically meaningful goals of treatments for neurodegenerative diseases. Ageing is the primary risk factor for neurodegenerative diseases and their associated comorbidities, such as vascular pathologies, in elderly individuals. Thus, we aim to elucidate the role of ageing in neurodegenerative diseases from the perspective of a complex system, in which the brain is the core and peripheral organs and tissues form a holistic network to support brain functions. During ageing, the progressive deterioration of the structure and function of the entire body hampers its active and adaptive responses to various stimuli, thereby rendering individuals more vulnerable to neurodegenerative diseases. Consequently, we propose that the prevention and treatment of neurodegenerative diseases should be grounded in holistic antiageing and rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach is a promising strategy to effectively prevent, pause or slow down the progression of neurodegenerative diseases.
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