Plasma infused into porcine cerebral white matter induces both acute interstitial and delayed vasogenic edema. Edematous white matter contains extracellular plasma proteins and rapidly induces oxidative stress as evidenced by increased protein carbonyl formation and heme oxygenase-1 induction. We tested the hypothesis that edematous white matter would also upregulate pro-inflammatory cytokine gene expression and develop DNA damage. We infused autologous plasma into the frontal hemispheric white matter of pentobarbital-anesthetized pigs. We monitored and controlled physiological variables and froze brains in situ at 1, 4 or 24 hrs. We determined edema volumes by computer-assisted morphometry. We measured white matter protein carbonyl formation by immunoblotting, cytokine gene expression by standard RT-PCR methods and DNA fragmentation by agarose gel electrophoresis. White matter edema developed acutely (1 hr) after plasma infusion and increased significantly in volume between 4 and 24 hrs. Protein carbonyl formation also occurred rapidly in edematous white matter with significant elevations (3 to 4-fold) already present at 1 hr. This increase remained through 24 hrs. Pro-inflammatory cytokine gene expression was also rapidly increased at 1 hr post-infusion. Evidence for DNA fragmentation began at 2 to 4 hrs, and a pattern indicative of both ongoing necrosis and apoptosis was robust by 24 hrs. Plasma protein accumulation in white matter induces acute edema development and a cascade of patho-chemical events including oxidative stress, pro-inflammatory cytokine gene expression and DNA damage. These results suggest that in diseases with increased blood-brain barrier (BBB) permeability or following intracerebral hemorrhage or traumatic brain injury, interstitial plasma can rapidly damage white matter.

4125X-ray Crystal Structure Analysis of 14. Suitable crystals of 14 formed from ethyl acetate-hexane mixtures with space group symmetry of P1 and cell constants of a = 9.699 (2) A, b = 12.688 (4) A, c = 8.122 (3) A, cy = 96.41 (3)O, /3 = 110.88 (2)O, and y = 77.74 (2)' for Z = 2 and a calculated density of 1.353 g/cm3. Of the 2503 reflections measured with an automatic four-circle diffractometer equipped with Cu radiation, 2138 were observed ( I 1 3u4. The function Cw(lFoI -lFc1)2 was minimized to give an unweighted residual of 0.057. Tables IV, V, and VI containing the final fractional coordinates, temperature parameters, bond distances, and bond angles are available as supplementary material.Acknowledgment. We thank Drs. S. Danishefsky, G. Hartman, and D. Claremon for helpful discussions held during the course of this work. We are indebted to John Moreau for microanalytical combusion analysis, J. Murphy for selected NMR spectra, and M. Banker for typing the manuscript. Dr. S. Pitzenberger carried out the NMR studies on 9 and 13.Registry No. -[ 1,3-dithian-2-yl]-5-nitrobenzyl alcohol, 98015-14-6; 2-[ 1,3-dithian-2-yl]-5-nitrobenzaldehyde, 98015-15-7.'3c chemical shifts of /3-carbon atoms in 17 series of substituted styrenes have been used to establish u13 substituent constants for nine para and seven meta substituents. The u13 values are similar to u+ values for electron-donating substituents, but are somewhat elevated for the cyano and nitro groups in both meta and para positions. Despite this, the use of mixed constants, u' for electron donors and u-for electron withdrawers, does not enhance the correlations. In dual substituent parameter (DSP) treatments, Swain's field and resonance parameters, F and R, give very slightly better correlations than do Taft's parameters, U I and any one of the four standard uR scales. The Swain and Taft approaches agree closely on the relative amounts of electron supply and demand through resonance and field effects. The u13 scale based on @-carbon shifts fails completely to correlate the shifts of the a-carbon atoms. In this case, Swain's parameters are clearly superior to any combination of the Taft sets. These results suggest that, at least for the 289 compounds comprising the data set reported here, the use of multiple resonance scales in DSP treatments is perhaps unjustified.

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