Browsing by Author "Romine, Jennifer"

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    Controlled cortical impact model for traumatic brain injury
    (JoVE, 2014-08-05) Romine, Jennifer; Gao, Xiang; Chen, Jinhui; Department of Neurological Surgery, IU School of Medicine
    Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.
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    Enhancing Neurogenesis in the Aging Brain through mTOR Pathway Activation
    (Office of the Vice Chancellor for Research, 2013-04-05) Romine, Jennifer; Gao, Xiang
    The U.S. population is aging. Age-related cognitive decline is a major public health problem. Developing an approach to treat or delay cognitive decline is critical. Neurogenesis by neural stem/progenitor cells (NSCs) in the hippocampus is related to cognitive function, and is greatly affected by the aging process. The molecular signaling that regulates age-related decline in neurogenesis is still poorly understood. Here we took the advantage of a transgenic mouse, Nestin-GFP, to assess neurogenesis and molecular signaling related to age-related decline in neurogenesis. We found that the total number of NSCs, including quiescent neural progenitors (QNPs) and amplifying neural progenitors (ANPs) decreased as the mice aged, but more importantly, ANPs are more significantly affected than QNPs, leading to further reduction in number and proliferation of ANPs. We further found that the mTOR signaling pathway is impaired in NSCs as mice age. Activating the mTOR signaling pathway through Ketamine injections increased NSC proliferation in aged mice. In contrast, inhibiting the activity of the mTOR signaling pathway by rapamycin is sufficient to reduce ANP proliferation in young mice. These results indicate that NSCs become more quiescent when the activity of mTOR signaling is compromised in aged mice, and stimulating the activity of mTOR signaling can overcome the age-associated decline in NSC proliferation. Following stimulation of the mTOR signaling pathway with Ketamine, we found a significant increase in the number of mature neurons. In order to determine whether or not a further increase in hippocampal neurogenesis is possible, we will next examine the ratio of newborn neuron survival.
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    OVERCOMING THE AGE-ASSOCIATED DECLINE IN NEURAL STEM CELL PROLIFERATION
    (Office of the Vice Chancellor for Research, 2012-04-13) Romine, Jennifer; Gao, Xiang; Chen, Jinhui
    The U.S. population is aging. Age-related cognitive decline is a major public health problem. Developing an approach to treat or delay cognitive decline is critical. Neurogenesis by neural stem/progenitor cells (NSCs) in the hippocampus is related to cognitive function, and is greatly affected by the aging process. The molecular signaling that regulates age-related decline in neurogenesis is still poorly understood. Here we took the advantage of a transgenic mouse, Nestin-GFP, to assess neurogenesis and molecular signal-ing related to age-related decline in neurogenesis. We found that the total number of NSCs, including quiescent neural progenitors (QNPs) and amplify-ing neural progenitors (ANPs) decreased as the mice aged, but more im-portantly, ANPs are more significantly affected than QNPs, leading to further reduction in number and proliferation of ANPs. We further found that the mTOR signaling pathway is impaired in NSCs as mice age. Activating the mTOR signaling pathway through Ketamine injections increased NSC prolif-eration in aged mice. In contrast, inhibiting the activity of the mTOR signal-ing pathway by rapamycin is sufficient to reduce ANP proliferation in young mice. These results indicate that NSCs becomes more quiescent when the activity of mTOR signaling is compromised in aged mice, and stimulating the activity of mTOR signaling can overcome the age-associated decline in NSC proliferation. This data suggests that promoting stem cell proliferation to en-hance neurogenesis may be a potential approach for attenuating cognitive decline in the aging brain.This work was supported by funding from the Ralph W. and Grace M. Showalter Research Award, Indiana University Biological Research Grant, NIH grants RR025761 and 1R21NS072631-01A, and Undergraduate Research Opportunities Program (UROP).