A5049938481- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Neurological Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Neonatal and fetal brain pathology
- Glioma Diagnosis and Treatment
- Retinal Diseases and Treatments
- MicroRNA in disease regulation
- Barrier Structure and Function Studies
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Neurological Disorders and Treatments
- Autophagy in Disease and Therapy
- S100 Proteins and Annexins
- Traumatic Brain Injury and Neurovascular Disturbances
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Adenosine and Purinergic Signaling
- Cancer-related molecular mechanisms research
- Retinal Imaging and Analysis
- Glaucoma and retinal disorders
- Pancreatic function and diabetes
- Alzheimer's disease research and treatments
University of Pittsburgh
2016-2025
VA Pittsburgh Healthcare System
2014-2025
Tianjin University of Science and Technology
2020-2025
Anhui University of Traditional Chinese Medicine
2024-2025
Harbin Medical University
2014-2025
Third Affiliated Hospital of Harbin Medical University
2025
Geriatric Research Education and Clinical Center
2014-2024
Institute for Neurodegenerative Disorders
2017-2024
Shanghai Jiao Tong University
2014-2024
Shanghai First People's Hospital
2020-2024
Background: Recent population studies have suggested that children with multiple exposures to anesthesia and surgery at an early age are increased risk of cognitive impairment.The authors therefore established animal model single versus anesthetic(s) in young adult mice, aiming distinguish the role different types impairment.Methods: Six-and 60-day-old mice were exposed various regimens.The then determined effects on learning memory function, levels proinflammatory cytokine interleukin-6...
Neuropathic pain is a common problem following spinal cord injury (SCI). Effective analgesic therapy has been hampered by the lack of knowledge about mechanisms underlying post‐SCI neuropathic pain. Current evidence suggests GABAergic nociceptive processing critical functional node in this complex phenotype, representing potential target for therapeutic intervention. Normal GABA neurotransmission dependent on precise regulation level intracellular chloride, which determined coordinated...
Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes. However, their functions cerebral ischemia remain largely unknown. Through an lncRNA array analysis rat model focal ischemia/reperfusion (I/R), we have identified CAMK2D-associated transcript 1 (C2dat1) as novel I/R-induced that regulated the expression CaMKIIδ murine models ischemia. C2dat1 mRNA was upregulated time-dependent manner mouse cortical penumbra after...
WNK kinases, including WNK3, and the associated downstream Ste20/SPS1-related proline-alanine-rich protein kinase (SPAK) oxidative stress responsive 1 (OSR1) comprise an important signaling cascade that regulates cation-chloride cotransporters. Ischemia-induced stimulation of bumetanide-sensitive Na(+)-K(+)-Cl(-) cotransporter (NKCC1) plays role in pathophysiology experimental stroke, but mechanism its regulation this context is unknown. Here, we investigated WNK3-SPAK/OSR1 pathway as a...
T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but relevant cell–derived mediators tissue injury remain unknown. Using a mouse model transient focal brain ischemia, we report that IL-21 is highly up-regulated in injured after ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation within 24 h reperfusion. Intracellular cytokine staining adoptive transfer experiments revealed...
Abstract The SLC12A cation-Cl − cotransporters (CCC), including NKCC1 and the KCCs, are important determinants of brain ionic homeostasis. SPAK kinase ( STK39 ) is CCC master regulator, which stimulates influx inhibits KCC-mediated efflux via phosphorylation at conserved, shared motifs. Upregulation SPAK-dependent has been implicated in several neurological diseases. Using a scaffold-hybrid strategy, we develop novel potent selective inhibitor,...
We investigated the effects of administration docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion in Sprague Dawley rats. Either DHA (16 mg/kg dimethyl sulfoxide) or vehicle sulfoxide (1 ml/kg) administered intraperitonially at 5 min after TBI, followed a daily dose for 3 to 21 days. triggered activation microglia macrophages, detected an increase Iba1 positively stained macrophages peri-lesion tissues 3, 7, and...
Glioblastoma is a highly malignant and incurable brain tumor characterized by intrinsic adaptive resistance to immunotherapies. However, how glioma cells induce immunosuppression escape immunosurveillance remains poorly understood. Here, we find upregulation of cancer-intrinsic Chitinase-3-like-1 (CHI3L1) signaling modulating an immunosuppressive microenvironment reprogramming tumor-associated macrophages (TAMs). Mechanistically, CHI3L1 binding with Galectin-3 (Gal3) selectively promotes TAM...
New research shows that disease-associated microglia in neurodegenerative brains present features of elevated phagocytosis, lysosomal functions, and lipid metabolism, which benefit brain repair. The underlying mechanisms remain poorly understood. Intracellular pH (pHi) is important for regulating aerobic glycolysis microglia, where Na/H exchanger (NHE1) a key regulator by extruding H+ exchange Na+ influx. We report here post-stroke Cx3cr1-CreER+/-;Nhe1flox/flox (Nhe1 cKO) displayed...
Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na + /H exchanger-1 (NHE1) reactive astrocytes astrocytic hypertrophy swelling. In this study, we examined role NHE1 protein astrogliosis, demyelination, function a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice...
Diabetic retinopathy (DR) and other diabetic vascular complications are the leading cause of death disability in patients with suboptimum glycemic control. In pathogenesis diseases, hyperglycemia-induced oxidative stress, DNA damage, poly-ADP-ribose-polymerase (PARP) hyperactivation play important roles endothelial cell impairment. Adipose differentiation-related protein FBXW7 was reported to regulate PGC-1α stability mitochondrial homeostasis. Here, we investigated role mechanism repairing...
We reported previously that inhibition of Na + -K -Cl − cotransporter isoform 1 (NKCC1) by bumetanide abolishes high extracellular K concentration ([K ] o )-induced swelling and intracellular Cl accumulation in rat cortical astrocytes. In this report, we extended our study using astrocytes from NKCC1-deficient (NKCC1 −/− ) mice. NKCC1 protein activity were absent [K 75 mM increased approximately fourfold +/+ cells ( P< 0.05) but had no effect Intracellular was 70% under P < remained...
We hypothesized that high extracellular K + concentration ([K ] o )-mediated stimulation of Na -K -Cl − cotransporter isoform 1 (NKCC1) may result in a net gain and Cl thus lead to high-[K -induced swelling glutamate release. In the current study, relative cell volume changes were determined astrocytes. Under 75 mM [K o, astrocytes swelled by 20.2 ± 4.9%. This -mediated was abolished NKCC1 inhibitor bumetanide (10 μM, 1.0 3.1%; P < 0.05). Intracellular 36 accumulation increased from...
We previously demonstrated that pharmacological inhibition of Na + −K −Cl − cotransporter isoform 1 (NKCC1) is neuroprotective in vivo and vitro ischemic models. In this study, we investigated whether genetic ablation NKCC1 provides neuroprotection after ischemia. Focal ischemia was induced by 2 hours occlusion the left middle cerebral artery (MCAO) followed 10 or 24 reperfusion. Two MCAO ten twenty-four reperfusion caused infarction (˜85 mm 3 ) wild-type (NKCC1 +/+ mice. Infarction volume...