Research progress on the role of hormones in ischemic stroke.

Ischemic stroke is a major cause of death and disability around the world. However, ischemic stroke treatment is currently limited, with a narrow therapeutic window and unsatisfactory post-treatment outcomes. Therefore, it is critical to investigate the pathophysiological mechanisms following ischemic stroke brain injury. Changes in the immunometabolism and endocrine system after ischemic stroke are important in understanding the pathophysiological mechanisms of cerebral ischemic injury. Hormones are biologically active substances produced by endocrine glands or endocrine cells that play an important role in the organism's growth, development, metabolism, reproduction, and aging. Hormone research in ischemic stroke has made very promising progress. Hormone levels fluctuate during an ischemic stroke. Hormones regulate neuronal plasticity, promote neurotrophic factor formation, reduce cell death, apoptosis, inflammation, excitotoxicity, oxidative and nitrative stress, and brain edema in ischemic stroke. In recent years, many studies have been done on the role of thyroid hormone, growth hormone, testosterone, prolactin, oxytocin, glucocorticoid, parathyroid hormone, and dopamine in ischemic stroke, but comprehensive reviews are scarce. This review focuses on the role of hormones in the pathophysiology of ischemic stroke and discusses the mechanisms involved, intending to provide a reference value for ischemic stroke treatment and prevention.

Role of lipocalin-2 in surgery-induced cognitive decline in mice: a signal from neuron to microglia.

BACKGROUND: Perioperative neurocognitive disorders (PNDs) are common complications observed among surgical patients. Accumulating evidence suggests that neuroinflammation is one of the major contributors to the development of PNDs, but the underlying mechanisms remain unclear. METHODS: qPCR and ELISA analysis were used for detecting LCN2 and cytokine levels. cx3cr1CreER/-:: R26iDTR/- crossed mouse line was used for microglia depletion; intracranial injection of recombinant LCN2 (rLCN2) and adeno-associated viruses (AAV)-mediated shRNA silencing approaches were used for gain and loss of function, respectively. Combing with in vitro microglia cell culture, we have studied the role of LCN2 in surgery-induced cognitive decline in mice. RESULTS: We revealed that Lcn2 mRNA and protein levels were greatly increased in mouse hippocampal neurons after surgery. This surgery-induced elevation of LCN2 was independent of the presence of microglia. Gain of function by intracranial injection of rLCN2 protein into hippocampus disrupted fear memory in naive mice without surgery. Conversely, silencing LCN2 in hippocampus by AAV-shRNA protected mice from surgery-induced microglia morphological changes, neuroinflammation and cognitive decline. In vitro, application of rLCN2 protein induced the expression of several pro-inflammatory cytokines in both BV-2 and primary microglia culture. CONCLUSIONS: These data suggest LCN2 acts as a signal from neuron to induce proinflammatory microglia, which contributes to surgery-induced neuroinflammation and cognitive decline in mice.

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy.

Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.