Diffusion tensor imaging correlates with cytopathology in a rat model of neonatal hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Diffusion tensor imaging (DTI) is a non-invasive MRI technique that has been used to quantify CNS abnormalities in various pathologic conditions. This study was designed to quantify the anisotropic diffusion properties in the brain of neonatal rats with hydrocephalus (HCP) and to investigate association between DTI measurements and cytopathology.</p> <p>Methods</p> <p>DTI data were acquired between postnatal day 7 (P7) and P12 in 12 rats with HCP induced at P2 and in 15 age-matched controls. Animals were euthanized at P11 or P22/P23 and brains were processed with immunohistochemistry for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule (Iba-1), and luxol fast blue (LFB) to assess astrocytosis, microglial reactivity and degree of myelination, respectively.</p> <p>Results</p> <p>Hydrocephalic rats were consistently found to have an abnormally low (at corrected <it>p</it>-level of <0.05) fractional anisotropy (FA) value and an abnormally high mean diffusivity (MD) value in the cerebral cortex (CX), the corpus callosum (CC), and the internal capsule (IC). Immunohistochemical analysis demonstrated trends of increasing astrocyte and microglial reactivity in HCP rats at P11 that reached statistical significance at P22/P23. A trend toward reduced myelination in the HCP rats was also found at P22/P23. Correlation analysis at P11 for the CC demonstrated statistically significant correlations (or trends) between the DTI measurement (the decreased FA and increased MD values) and the GFAP or Iba-1 rankings. The immunohistochemical rankings in the IC at P22/P23 were also significantly correlated or demonstrated a trend with both FA and MD values.</p> <p>Conclusions</p> <p>This study demonstrates the feasibility of employing DTI on the brain in experimental hydrocephalus in neonatal rats and reveals impairments in multiple regions of interest in both grey and white matter. A strong correlation was found between the immunohistochemical results and the changes in anisotropic diffusion properties.</p

Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP.</p> <p>Results</p> <p>When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.</p> <p>Conclusion</p> <p>Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.</p

Racialized risk environments in a large sample of people who inject drugs in the United States

BACKGROUND: Substantial racial/ethnic disparities exist in HIV infection among people who inject drugs (PWID) in many countries. To strengthen efforts to understand the causes of disparities in HIV-related outcomes and eliminate them, we expand the “Risk Environment Model” to encompass the construct “racialized risk environments,” and investigate whether PWID risk environments in the United States are racialized. Specifically, we investigate whether black and Latino PWID are more likely than white PWID to live in places that create vulnerability to adverse HIV-related outcomes. METHODS: As part of the Centers for Disease Control and Prevention’s National HIV Behavioral Surveillance, 9,170 PWID were sampled from 19 metropolitan statistical areas (MSAs) in 2009. Self-reported data were used to ascertain PWID race/ethnicity. Using Census data and other administrative sources, we characterized features of PWID risk environments at four geographic scales (i.e., ZIP codes, counties, MSAs, and states). Means for each feature of the risk environment were computed for each racial/ethnic group of PWID, and were compared across racial/ethnic groups. RESULTS: Almost universally across measures, black PWID were more likely than white PWID to live in environments associated with vulnerability to adverse HIV-related outcomes. Compared to white PWID, black PWID lived in ZIP codes with higher poverty rates and worse spatial access to substance abuse treatment and in counties with higher violent crime rates. Black PWID were less likely to live in states with laws facilitating sterile syringe access (e.g., laws permitting over-the-counter syringe sales). Latino/white differences in risk environments emerged at the MSA level (e.g., Latino PWID lived in MSAs with higher drug-related arrest rates). CONCLUSION: PWID risk environments in the US are racialized. Future research should explore the implications of this racialization for racial/ethnic disparities in HIV-related outcomes, using appropriate methods