Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

Role of lipocalin 2 in stroke.

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

The Role of Pericytes in Ischemic Stroke: Fom Cellular Functions to Therapeutic Targets.

Ischemic stroke (IS) is a cerebrovascular disease causing high rates of disability and fatality. In recent years, the concept of the neurovascular unit (NVU) has been accepted by an increasing number of researchers and is expected to become a new paradigm for exploring the pathogenesis and treatment of IS. NVUs are composed of neurons, endothelial cells, pericytes, astrocytes, microglia, and the extracellular matrix. As an important part of the NVU, pericytes provide support for other cellular components and perform a variety of functions, including participating in the maintenance of the normal physiological function of the blood-brain barrier, regulating blood flow, and playing a role in inflammation, angiogenesis, and neurogenesis. Therefore, treatment strategies targeting pericyte functions, regulating pericyte epigenetics, and transplanting pericytes warrant exploration. In this review, we describe the reactions of pericytes after IS, summarize the potential therapeutic targets and strategies targeting pericytes for IS, and provide new treatment ideas for ischemic stroke.