Purpose: To determine the change over time of the apparent diffusion coefficient (ADC) and relative anisotropy of cerebral water in a cohort of premature newborns serially studied near birth and again near term. Materials and Methods:Newborns were classified as normal (N ϭ 11), minimal white matter injury (N ϭ 7), or moderate white matter injury (N ϭ 5).Results: ADC decreased significantly with age in all brain regions in newborns classified as normal and those with minimal white matter injury. ADC increased with age or failed to decline in widespread areas of white matter in newborns with moderate white matter injury. Anisotropy increased with age in all white matter regions in newborns classified as normal. Anisotropy did not increase in frontal white matter in those with minimal white matter injury, and in widespread white matter areas in those with moderate white matter injury. Conclusion:This study demonstrates that serial diffusion tensor magnetic resonance imaging scans of premature newborns can detect differences in white matter maturation in infants with and without white matter injury.

Hypoglycemic detection at the portal-mesenteric vein (PMV) appears mediated by spinal afferents and is critical for the counter-regulatory response (CRR) to slow-onset, but not rapid-onset, hypoglycemia. Since rapid-onset hypoglycemia induces Fos protein expression in discrete brain regions, we hypothesized that denervation of the PMV or lesioning spinal afferents would suppress Fos expression in the dorsal medulla during slow-onset hypoglycemia, revealing a central nervous system reliance on PMV glucosensors. Rats undergoing PMV deafferentation via capsaicin, celiac-superior mesenteric ganglionectomy (CSMG), or total subdiaphragmatic vagotomy (TSV) were exposed to hyperinsulinemic–hypoglycemic clamps where glycemia was lowered slowly over 60–75 min. In response to hypoglycemia, control animals demonstrated a robust CRR along with marked Fos expression in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Fos expression was suppressed by 65–92% in capsaicin-treated animals, as was epinephrine (74%), norepinephrine (33%), and glucagon (47%). CSMG also suppressed Fos expression and CRR during slow-onset hypoglycemia, whereas TSV failed to impact either. In contrast, CSMG failed to impact upon Fos expression or the CRR during rapid-onset hypoglycemia. Peripheral glucosensory input from the PMV is therefore required for activation of hindbrain neurons and the full CRR during slow-onset hypoglycemia.

Matveyenko AV, Bohland MA, Saberi M, Donovan CM. Portal vein hypoglycemia is essential for full induction of hypoglycemiaassociated autonomic failure with slow-onset hypoglycemia. Am J Physiol Endocrinol Metab 293: E857-E864, 2007. First published July 17, 2007; doi:10.1152/ajpendo.00283.2007.-Antecedent hypoglycemia leads to impaired counterregulation and hypoglycemic unawareness. To ascertain whether antecedent portal vein hypoglycemia impairs portal vein glucose sensing, thereby inducing counterregulatory failure, we compared the effects of antecedent hypoglycemia, with and without normalization of portal vein glycemia, upon the counterregulatory response to subsequent hypoglycemia. Male Wistar rats were chronically cannulated in the carotid artery (sampling), jugular vein (glucose and insulin infusion), and mesenteric vein (glucose infusion). On day 1, the following three distinct antecedent protocols were employed: 1) HYPO-HYPO: systemic hypoglycemia (2.52 Ϯ 0.11 mM); 2) HYPO-EUG: systemic hypoglycemia (2.70 Ϯ 0.03 mM) with normalization of portal vein glycemia (portal vein glucose ϭ 5.86 Ϯ 0.10 mM); and 3) EUG-EUG: systemic euglycemia (6.33 Ϯ 0.31 mM). On day 2, all groups underwent a hyperinsulinemic-hypoglycemic clamp in which the fall in glycemia was controlled so as to reach the nadir (2.34 Ϯ 0.04 mM) by minute 75. Counterregulatory hormone responses were measured at basal (Ϫ30 and 0) and during hypoglycemia (60 -105 min). Compared with EUG-EUG, antecedent hypoglycemia (HYPO-HYPO) significantly blunted the peak epinephrine (10.44 Ϯ 1.35 vs. 15.75 Ϯ 1.33 nM: P ϭ 0.01) and glucagon (341 Ϯ 16 vs. 597 Ϯ 82 pg/ml: P ϭ 0.03) responses to next-day hypoglycemia. Normalization of portal glycemia during systemic hypoglycemia on day 1 (HYPO-EUG) prevented blunting of the peak epinephrine (15.59 Ϯ 1.43 vs. 15.75 Ϯ 1.33 nM: P ϭ 0.94) and glucagon (523 Ϯ 169 vs. 597 Ϯ 82 pg/ml: P ϭ 0.66) responses to day 2 hypoglycemia. Consistent with hormonal responses, the glucose infusion rate during day 2 hypoglycemia was substantially elevated in HYPO-HYPO (74 Ϯ 12 vs. 49 Ϯ 4 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ; P ϭ 0.03) but not HYPO-EUG (39 Ϯ 7 vs. 49 Ϯ 4 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 : P ϭ 0.36). Antecedent hypoglycemia local to the portal vein is required for the full induction of hypoglycemiaassociated counterregulatory failure with slow-onset hypoglycemia. glucose sensor; sympathoadrenal; counterregulation INTENSIVE INSULIN REPLACEMENT therapy has proven to be an effective tool in the reduction of mean plasma glycemia and subsequent prevention of microvascular and macrovascular complications in patients with type 1 diabetes (T1DM) and late-stage type 2 diabetes (14, 34). However, intensive glucose management is associated with increased frequency of iatrogenic hypoglycemia (14), which results in increased morbidity and has been described as the major obstacle in the management of the disease (6). In diabetes, hypoglycemia results from imperfect insulin replacement combined with an impaired sympathoadrenal response, absent glucagon secretion, a...