Glial activation and neuroinflammation occur in neurodegenerative disease and brain injury, however their presence in normal brain aging suggests that chronic neuroinflammation may be a factor in agerelated dementia. Few studies have investigated the impact of sustained elevation of hippocampal interleukin-1β, a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on cognition in mice. We utilized the IL-1β XAT transgenic mouse to initiate bilateral hippocampal overexpression of interleukin-1β to determine the influence of sustained neuroinflammation independent of disease pathology. Fourteen days following transgene induction, adult male and female IL-1β XAT mice were tested on non-spatial and spatial versions of the Morris water maze. For the spatial component, one retention trial was conducted forty-eight hours after completion of a 3-day acquisition protocol (8 trials per day). Induction of IL-1β did not impact non-spatial learning, but was associated with delayed acquisition and decreased retention of the spatial task. These behavioral impairments were accompanied by robust reactive gliosis and elevated mRNA expression of inflammatory genes in the hippocampus. Our results suggest that prolonged neuroinflammation response per se may impact mnemonic processes and support the future application of IL-1β XAT transgenic mice to investigate chronic neuroinflammation in age-and pathology-related cognitive dysfunction. Keywordsneuroinflammation; water maze; IL-1β XAT transgenic mouse; hippocampus Chronic neuroinflammation is a prominent feature of Alzheimer's disease (AD) and is believed to contribute to the molecular cascade that ultimately manifests as cognitive dysfunction. It is well known that the single most important risk factor for AD is age. One reason for this association is that the progression from initial pathophysiological event to clinical detection is *Corresponding author: Amy H. Moore, Ph.D., Department of Biology, Carleton College, One North College Street, Northfield, MN 55057, Phone: 1.507.222.5981, Fax: 1.507.222.5757, amoore@carleton.edu. Neuroscience Section Editor: Behavioral Neuroscience Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 December 29. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript likely to be on the order of decades. Although glial activation is influenced by neuronal plaques and tangles, its presence in the aged brain (Nichols et al., 1993;P...

With the advent and emerging importance of neurobiology and its relation to behavior, scientists desire the capability to apply noninvasive, quantitative imaging of neuronal activity to small rodents. To this end, the authors' laboratory has developed microPET, a high-resolution positron emission tomography (PET) scanner that is capable of performing in vivo molecular imaging at a resolution sufficient to resolve major structures in the rat brain. The authors report in this article that, in conjunction with 2-[18F]fluoro-2-deoxyglucose (FDG), microPET provides accurate rates of cerebral glucose metabolism (59.7 to 108.5 micromol/100 g x min) in conscious adult rats as validated by within-subject autoradiographic measurements (59.5 to 136.2 micromol/100 g x min; r = 0.88; F[1,46] = 168.0; P < 0.001). By conducting repeated quantitative scanning, the authors demonstrate the sensitivity and accuracy of FDG-microPET to detect within-subject metabolic changes induced by traumatic brain injury. In addition, the authors report that longitudinal recovery from traumatic brain injury-induced metabolic depression, as measured by quantitative FDG-microPET, is significantly correlated (r = 0.65; P < 0.05) to recovery of behavioral dysfunction, as assessed by the Morris Water Maze performance of the same rats, after injury. This is the first study to demonstrate that FDG-microPET is quantitative, reproducible, and sensitive to metabolic changes, introducing a new approach to the longitudinal study of small animal models in neuroscience research.

This study was designed to determine the regional and temporal profile of 45calcium (45Ca2+) accumulation following mild lateral fluid percussion (LFP) injury and how this profile differs when traumatic brain injury occurs early in life. Thirty-six postnatal day (P) 17, thirty-four P28, and 17 adult rats were subjected to a mild (approximately 2.75 atm) LFP or sham injury and processed for 45Ca2+ autoradiography immediately, 6 h, and 1, 2, 4, 7, and 14 days after injury. Optical densities were measured bilaterally within 16 regions of interest. 45Ca2+ accumulation was evident diffusely within the ipsilateral cerebral cortex immediately after injury (18-64% increase) in all ages, returning to sham levels by 2-4 days in P17s, 1 day in P28s, and 4 days in adults. While P17s showed no further 45Ca2+ accumulation, P28 and adult rats showed an additional delayed, focal accumulation in the ipsilateral thalamus beginning 2-4 days postinjury (12-49% increase) and progressing out to 14 days (26-64% increase). Histological analysis of cresyl violet-stained, fresh frozen tissue indicated little evidence of neuronal loss acutely (in all ages), but considerable delayed cell death in the ipsilateral thalamus of the P28 and adult animals. These data suggest that two temporal patterns of 45Ca2+ accumulation exist following LFP: acute, diffuse calcium flux associated with the injury-induced ionic cascade and blood brain barrier breakdown and delayed, focal calcium accumulation associated with secondary cell death. The age-dependency of posttraumatic 45Ca2+ accumulation may be attributed to differential biomechanical consequences of the LFP injury and/or the presence or lack of secondary cell death.

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