Leveraging single-cell RNA sequencing to unravel the impact of aging on stroke recovery mechanisms in mice.

Aging compromises the repair and regrowth of brain vasculature and white matter during stroke recovery, but the underlying mechanisms remain elusive. To understand how aging jeopardizes brain tissue repair after stroke, we performed single-cell transcriptomic profiling of young adult and aged mouse brains at acute (3 d) and chronic (14 d) stages after ischemic injury, focusing a priori on the expression of angiogenesis- and oligodendrogenesis-related genes. We identified unique subsets of endothelial cells (ECs) and oligodendrocyte (OL) progenitors in proangiogenesis and pro-oligodendrogenesis phenotypic states 3 d after stroke in young mice.

Poststroke Intravenous Transplantation of Human Mesenchymal Stem Cells Improves Brain Repair Dynamics and Functional Outcomes in Aged Mice.

Background: Stroke is the primary cause of chronic disability in the elderly, as there are no neurorestorative treatments for those who do not qualify for recanalization therapy. Experimental evidence in stroke animals suggests that transplantation of bone marrow-derived human mesenchymal stem cells (hMSCs) holds promise, but hMSC transplantation has not been systematically tested in aged animals. We tested the hypothesis that poststroke hMSC transplantation improves stroke recovery in aged mice by promoting brain repair.

Selective brain hypothermia attenuates focal cerebral ischemic injury and improves long-term neurological outcome in aged female mice.

Aims: This study aimed to investigate the effects of mild selective brain hypothermia on aged female ischemic mice.

Methods: A distal middle cerebral artery occlusion (dMCAO) model was established in aged female mice, who were then subjected to mild selective brain hypothermia immediately after the dMCAO procedure. Neurological behavioral examinations were conducted prior to and up to 35 days post-ischemia.

Neuroprotection against ischemic stroke requires a specific class of early responder T cells in mice.

Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution.

Adiponectin ameliorates hypoperfusive cognitive deficits by boosting a neuroprotective microglial response.

Vascular cognitive impairment and dementia (VaD) is the second most common type of dementia caused by chronic vascular hypoperfusion. Adiponectin, one of the cytokines produced by adipocytes (adipocytokine), plays a role in CNS pathologies, but its specific function in VaD is unknown. Here, transcriptomic analyses on human brain tissues showed downregulation of adipocytokine/PPAR signaling in VaD patients, with prominent upregulation of pro-inflammatory responses.

Microglial/Macrophage polarization and function in brain injury and repair after stroke.

Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia and CNS-resident macrophages are rapidly activated and regulate neuropathological processes to steer the course of functional recovery. To accelerate this recovery, microglia can engulf dying cells and clear irreparably-damaged tissues, thereby creating a microenvironment that is more suitable for the formation of new neural circuitry.

Microglial Responses to Brain Injury and Disease: Functional Diversity and New Opportunities.

As an integral part of the innate immune system of the brain, resident microglia must react rapidly to the onset of brain injury and neurological disease. These dynamic cells then continue to shift their phenotype along a multidimensional continuum with overlapping pro- and anti-inflammatory states, allowing them to adapt to microenvironmental changes during the progression of brain disorders. However, the ability of microglia to shift phenotype through nimble molecular, structural, and functional changes comes at a cost, as the extreme pro-inflammatory states may prevent these professional phagocytes from clearing toxic debris and secreting tissue-repairing neurotrophic factors.

Plasma RANTES level is correlated with cardio-cerebral atherosclerosis burden in patients with ischemic cerebrovascular disease.

Background: Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a chemokine actively involved in the initiation and progression of atherosclerosis (AS), which is the major cause of ischemic cerebrovascular disease (ICVD). This study aimed to determine the associations between circulating RANTES level and overall AS conditions of cardiac and cerebral vessel beds in patients with ICVD.

Methods: Patients with ICVD admitted to the department of neurology of Xuanwu Hospital from April 1, 2019 to June 30, 2019 were prospectively enrolled in the study.