Area:
Neuroscience Biology, Ophthalmology, Oncology
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High-probability grants
According to our matching algorithm, Jeffrey W. Sall is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2010 — 2013 |
Sall, Jeffrey W. |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Volatile Anesthetic Alteration of Neural Precursor Cell Cycle and Fate Decisions @ University of California, San Francisco
DESCRIPTION (provided by applicant): The long-term goal of the PI is develop into an academic anesthesiologist with an independent research program focused on anesthetics and neural development. This proposal outlines a career development plan that includes didactic and laboratory based instruction in neural development and stem cell biology. During its course the PI will obtain several new skills necessary to compete for independent funding in this field in the future. The research and didactic program will be carried out at the University of California, San Francisco in the department of Anesthesia and Perioperative Care, one of the top departments in this field. All general anesthetics act in part at GABA or NMDA receptors and recent research has identified an important role for GABA and NMDA mediated signals in growth and differentiation of neural progenitor cells (NPCs). Therefore, volatile anesthetics acting at these known and other unknown sites may alter proliferation, differentiation and survival of NPCs with implications for long-term effects on CNS function. Neurogenesis in the hippocampal dentate gyrus is necessary for certain types of learning and memory. Our preliminary data show isoflurane decreases proliferation of NPCs both in vitro and in vivo and in rodents and we have observed a hippocampal cognitive deficit 3 weeks to 8 months after isoflurane exposure. We propose that long-term hippocampal-based cognitive deficits following anesthesia are a consequence of anesthetic induced changes in hippocampal NPCs. We will test the hypothesis that anesthetics induce cell cycle exit and premature differentiation in NPCs. Aim 1 will focus on mechanisms of anesthetic action on NPCs in vitro. Aim 2 will investigate changes in the cyto-architecture of the hippocampal dentate gyrus after anesthetic exposure in vivo. Together these aims will begin to define the effect of anesthetics on hippocampal development. PUBLIC HEALTH RELEVANCE: Recent identification of long-term cognitive deficits following general anesthesia in neonatal animals has caused significant concern for clinical practice. This proposal seeks to understand how anesthetics alter neural development and neural precursors in the hippocampus. )
|
0.976 |
2015 — 2019 |
Sall, Jeffrey W. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Testosterone's Role in Sex-Specific Outcomes After Early Anesthesia @ University of California, San Francisco
DESCRIPTION (provided by applicant): Sex differences in cognitive outcome after early childhood anesthesia have been poorly studied and no mechanism for such differences is known. The long-term goal of this laboratory is to improve the safety of anesthesia delivered to children by eliminating lasting cognitive effects from anesthetic-induced changes in the developing brain. The objective of this proposal is to identify specific sex related factors that lead to divergent cognitive outcomes in male and female rodents. The central hypothesis is that sex-specific cognitive outcomes after early anesthesia are due to testosterone-mediated delay of KCC2 expression which slows the transition from excitatory to inhibitory GABAergic signaling in the hippocampus of male rats leading to loss of neuronal spines and eventual cognitive dysfunction. This hypothesis will be tested in two specific aims: 1) Establish the role of testosterone in dendritic spinogenesis and cognitive outcome after neonatal anesthesia in rats. 2) Establish the role of testosterone in KCC2 expression and determine whether excitatory GABAergic neurotransmission is necessary for anesthetic-mediated spine loss and cognitive deficits. The first aim will compare dendritic spine densities of hippocampal pyramidal neurons and cognitive function following anesthesia exposure in male and female rats after gonadectomy and/or treatment with exogenous testosterone. Under the second aim, section 2.1, will define the role of testosterone in sex-specific temporal expression of KCC2 in control, male and female rats after gonadectomy or treatment with exogenous testosterone. And section 2.2, will use in utero electroporation, to genetically manipulate hippocampal excitatory signaling by early expression of KCC2 or the inward rectifying Kir2.1 (two mechanisms that inhibit GABAergic depolarization) then assess dendritic spine morphology and density as well as cognitive function after early anesthesia exposure. The approach is innovative because cellular level mechanistic studies are guided by and interpreted in light of cognitive function testing, the most relevant outcome that can be measured in animals. The expected contribution from these studies is a detailed understanding of the sex-specific factors leading to deficits of recognition memory in males' vs females after early anesthesia exposure. The proposed research is significant because 1)~ T of children anesthetized in the first three years of life are male, and 2)few other studies have investigated the role of sex in cognitive outcome after early anesthesia, and 3)there is no known mechanism for sex-specific cognitive outcomes after early childhood anesthesia exposure. The results obtained from the proposed research will lead to eventual trials to improve risk stratification and guide decision making around the youngest patients that must be exposed to anesthesia.
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0.976 |