Assessing long-term neuroinflammatory responses to encephalopathy using MRI approaches in a rat endotoxemia model.

Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24 h and 1 week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24 h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions. Increased MRI signal intensities were observed in LPS rat brains in cerebral cortex, perirhinal cortex, and hippocampus regions 1 week post-LPS. Long-term BBB dysfunction was detected in the cerebral cortex at 6 weeks post-LPS. Increased relative cerebral blood flow (rCBF) in cortex and thalamus regions at 24 h, decreased cortical and hippocampal rCBF at 6 weeks, decreased cortical rCBF at 3 and 12 weeks, and increased thalamus rCBF at 6 weeks post-LPS, were detected. MRS indicated that LPS-exposed rat brains had decreased: NAA/Cho metabolite ratios at 1, 3, 6, and 12 weeks; Cr/Cho at 1, 3, and 12 weeks; and Myo-Ins/Cho at 1, 3, and 6 weeks post-LPS. Free radical imaging detected increased radical levels in LPS rat brains at 24 h and 1 week post-LPS. LPS-exposed rats were compared to saline-treated controls. We clearly demonstrated BBB dysfunction, impaired vascularity, and decreased brain metabolites, as measures of long-term neuroinflammatory indicators, as well as increased free radicals in a LPS-induced rat SAE model.

Ultrastructural and histochemical studies of murine megacolon.

The myenteric plexus of the colon was studied ultrastructurally in a colony of an Ls Ls strain of mice manifesting a piebald coat color mutation associated with a high incidence of genetically determined aganglionic megacolon. Ultrastructural studies were histochemically supplemented by the Maillet technic and stains for acetylcholinesterase and catecholamines. The development of megacolon did not appear to require total aganglionosis, since ostensibly aganglionic areas contained rare ganglion cells. In the distal narrowed segment, both cholinergic and adrenergic fibers in the muscularis, submucosa and mucosa were somewhat reduced. In the mouse, the dilated portion showed an abrupt increase in adrenergic fibers. These findings are related to the pathophysiology of the disorder. The increasing degenerative changes seen in myenteric plexus structures from the fetus to adult suggest that aganglionic megacolon may be an abiotrophy, wherein the congenitally deficient myenteric plexus may be unusually predisposed to postnatal injury and degeneration.