quantification-neurovascular-protection-following-repetitive-hypoxic

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice

Experimental animal models of stroke are invaluable tools for understanding stroke pathology and developing more effective treatment strategies. A 2 week ...

University of Texas Southwestern Medical Center

To evaluate the potential for Mecobalamin as a neuroprotective agent in optic nerve crush injury.

The protective role of Mecobalamin following optic nerve crush in adult rats.

Glaucoma club: a successful model to educate glaucoma patients.

This study aims to compare retinal vessel anatomy of normal rhesus monkeys and humans and to provide a basis from a structural perspective for the use of rhesus monkey as an experimental model in future studies of retinal vessels.

Comparative study of the retinal vessel anatomy of rhesus monkeys and humans.

Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a rare disorder characterized by clonal proliferation and excess accumulation of pathologic Langerhans cells causing local or systemic effects. Bone is the most common organ involved and a single skull lesion is the most frequent presentation of childhood LCH. However, sphenoid sinus is an uncommon condition of involvement in LCH. Here we report a case of LCH in the sphenoid sinus, which occurred in a seven-year-old girl who presented initially with headache. The girl had suffered from headache for one month before she went to an otorhinolaryngologist one week before. Magnetic resonance imaging (MRI) showed a lesion of inflammatory granuloma. Surgery was performed and the disease was diagnosed pathologically as single-site LCH via hematoxylin-eosin (H&E) and immunohistochemical staining.

Langerhans cell histiocytosis of the sphenoid sinus: a case report.

Chronic hypoxia (CH) is a major risk factor for impaired cognitive function in various disease states, particularly in the context of cyanotic congenital heart disease. Although most brain development occurs prenatally, the dentate gyrus (DG) of the hippocampus harbors progenitor stem cells that contribute to its ongoing development postnatally. It is unclear how exposure to CH might affect postnatal hippocampal development, so we used a transgenic mouse that expresses enhanced green fluorescent protein (eGFP) within this progenitor population to determine the effect of CH on the DG. We find that exposure to 10% oxygen from postnatal d 3 to 28 results in a smaller DG with long-term impairment of hippocampal neurogenesis. Because the mammalian target of rapamycin (mTOR) pathway is a well-known regulator of cell proliferation and growth and is sensitive to hypoxia, we investigated its activation on exposure to CH and find it to be attenuated specifically in neural progenitor cells. Systemic inhibition of the mTOR pathway using rapamycin also caused impairment of hippocampal neurogenesis that mimics exposure to CH. Our findings demonstrate that CH results in long-term impairment of hippocampal neurogenesis and is mediated, in part, by attenuation of the mTOR pathway.

Chronic hypoxia impairs murine hippocampal development and depletes the postnatal progenitor pool by attenuating mammalian target of rapamycin signaling.

To identify the likelihood of family history as a risk factor for the presence and severity of primary angle closure (PAC) and primary open angle glaucoma (POAG) in a Chinese population.

Influence of family history as a risk factor on primary angle closure and primary open angle glaucoma in a Chinese population.

Brain injury is an important cause of morbidity in infants at risk for exposure to chronic hypoxia. Using a transgenic mouse that expresses green fluorescent protein (GFP) within this progenitor population we have previously shown that exposure to chronic hypoxia significantly decreases the progenitor stem cell pool in the dentate gyrus of the hippocampus that is in part mediated by inhibition of the mammalian target of rapamycin (mTOR) pathway. Hence we hypothesized that pharmacological inhibition of the mTOR pathway using rapamycin will alter the progenitor stem cell pool and impair the development of the dentate gyrus. We find that prolonged inhibition of the mTOR pathway causes a decrease in the early progenitor stem cell pool, demonstrated by decreased GFP-expressing progenitors, which persists long term. However there is a significant increase in proliferating progenitor cell pool, as seen by increased BrdU that is coupled with increased apoptosis thereby leading to fewer Neu N-expressing mature neurons. Further inhibition of the mTOR pathway leads to depletion of the astrocyte and microglial pool in the dentate gyrus as well. Overall our findings demonstrate that pharmacological inhibition of the mTOR pathway leads to impaired development of the DG, raising the concern that in young children could impair cognitive development.

Pharmacological inhibition of the mTOR pathway impairs hippocampal development in mice.

To identify familial aggregation of primary open angle glaucoma (POAG) in first-degree relatives in Shanghai, China.

Familial aggregation of primary open angle glaucoma in Shanghai, China.

The aim of this study was to assess the prevalence of psychological disturbances and personality traits in primary angle closure glaucoma (PACG) and primary open-angle glaucoma (POAG) patients.

Anxiety and Depression are More Prevalent in Primary Angle Closure Glaucoma Than in Primary Open-Angle Glaucoma.

Repetitive hypoxic preconditioning (RHP) creates an anti-inflammatory phenotype that protects from stroke-induced injury for months after a 2-week treatment. The mechanisms underlying long-term tolerance are unknown, though one exposure to hypoxia significantly increased peripheral B cell representation. For this study, we sought to determine if RHP specifically recruited B cells into the protected ischemic hemisphere, and whether RHP could phenotypically alter B cells prior to stroke onset.

Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke.

To evaluate the in vivo changes in the Schlemm's canal (SC) in patients with primary angle-closure glaucoma (PACG) after trabeculectomy using spectral-domain optical coherence tomography (SD-OCT).

Schlemm's canal expands after trabeculectomy in patients with primary angle-closure glaucoma.

Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.

Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms.

Using anterior chamber optical coherence tomography to evaluate changes in angle anatomy in patients with primary angle-closure glaucoma (PACG) before and after trabeculectomy.

Optical Coherence Tomography Assessment of Angle Anatomy Changes After Trabeculectomy in Primary Angle-Closure Glaucoma.

Chronic hypoxia (CH), a disease state that accounts for significant morbidity and mortality in pediatrics, occurs in many children during critical periods of hippocampal development and cortical myelination. Hippocampal neurogenesis occurs throughout postnatal life and is important for normal development, thus impairment results in long-term cognitive deficits. Erythropoietin (EPO), a drug commonly known for its role in erythrogenesis, has recently been evaluated in neuroprotection in neonatal injury models and preterm brain injury. However, the effects of EPO therapy on hippocampal neurogenesis and myelination in pediatric CH are unknown. We show that CH decreases hippocampal neurogenesis in a pediatric mouse model. This decrease in early and late progenitors, and actively dividing cells is rescued with EPO treatment. Furthermore, we show that CH during this critical time decreases oligodendrocyte progenitor (OPC) populations in the cortex, leading to defective myelination. However, EPO therapy is only able to rescue the OPC but not the loss of mature myelin. Overall, our findings demonstrate that CH in developing mice has significant effects on hippocampal neurogenesis and OPCs, which can be rescued with EPO treatment. Future studies should confirm the role of this FDA-approved therapy in neuroprotection in at-risk pediatric populations.

Article	Year
The protective role of Mecobalamin following optic nerve crush in adult rats. Yan ke xue bao = Eye science / "Yan ke xue bao" bian ji bu\| PubMed ID: 15499726	2004
Glaucoma club: a successful model to educate glaucoma patients. Clinical & experimental ophthalmology\| PubMed ID: 19702722	2009
Comparative study of the retinal vessel anatomy of rhesus monkeys and humans. Clinical & experimental ophthalmology\| PubMed ID: 20584020	2010
Langerhans cell histiocytosis of the sphenoid sinus: a case report. The Turkish journal of pediatrics\| PubMed ID: 21434545	2010
Chronic hypoxia impairs murine hippocampal development and depletes the postnatal progenitor pool by attenuating mammalian target of rapamycin signaling. Pediatric research\| PubMed ID: 21532529	2011
Influence of family history as a risk factor on primary angle closure and primary open angle glaucoma in a Chinese population. Ophthalmic epidemiology\| PubMed ID: 21961512	2011
Pharmacological inhibition of the mTOR pathway impairs hippocampal development in mice. Neuroscience letters\| PubMed ID: 23395832	2013
Familial aggregation of primary open angle glaucoma in Shanghai, China. Molecular vision\| PubMed ID: 24019742	2013
Anxiety and Depression are More Prevalent in Primary Angle Closure Glaucoma Than in Primary Open-Angle Glaucoma. Journal of glaucoma\| PubMed ID: 24240874	2013
Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke. Journal of neuroinflammation\| PubMed ID: 24485041	2014
Schlemm's canal expands after trabeculectomy in patients with primary angle-closure glaucoma. Investigative ophthalmology & visual science\| PubMed ID: 25118266	2014
Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spina... Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 25281717	2014
Optical Coherence Tomography Assessment of Angle Anatomy Changes After Trabeculectomy in Primary Angle-Closure Glaucoma. Journal of glaucoma\| PubMed ID: 25318576	2014
Erythropoietin-mediated neuroprotection in a pediatric mouse model of chronic hypoxia. Neuroscience letters\| PubMed ID: 25899777	2015

Xiangmei Kong

Biography

JoVE Journal Publications

Other Publications