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The progression of experimental spinal cord injury (SCI) was followed with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and neurobehavioral studies on postinjury days 0, 2, 4, 7, 10, 14, 17, 21, 28, 35, and 42. Gadopentate dimeglumine (Gd) was administered IV and postcontrast, T 1 -weighted, axial images were acquired repetitively for up to 60 min. Images were analyzed to determine the spatial and temporal evolution of the intensity enhancement. A statistical decision mechanism was developed to objectively detect the enhancement. Strong and rapid enhancement was observed at the epicenter of injury, indicating a significant compromise in blood spinal cord barrier. The enhanced regions in each slice were combined to estimate the area and volume of the lesion. On the day of injury, around 85% of the total cord area at the epicenter showed enhancement within the first 15 min of Gd administration. At the same time, the enhanced volumes attained nearly 40% of the total cord volume and extended axially over 8 mm along the cord. The blood-spinal cord barrier (BSCB) maintains a highly regulated homeostatic environment in the spinal cord (SC) tissue. This regulatory function is sustained by various structures, including the capillary endothelial tight junctions. Under normal physiological conditions, BSCB protects the cord tissue by exhibiting selective permeability to the constituents of intravascular fluid (1,2). A traumatic insult to SC disrupts the structural and biochemical integrity of BSCB. The altered tight junctional patency allows vesicular transport of toxic substances from blood plasma to interstitial spaces. This makes the SC tissue environment unfavorable for neuronal survival, and inhibits tissue repair processes and neurologic recovery. By following the changes in BSCB after injury, important information may be gained about the regions of initial SC tissue damage and a time window for effective drug delivery across the barrier. Assessing BSCB in the late phases of the injury may help evaluate the progression of spinal cord injury (SCI) as well as the efficacy of potential therapeutic interventions.Changes in BSCB permeability can be followed experimentally using intravascularly administered tracers (such as plasma proteins, radiolabeled proteins, and small-molecular-weight molecules) that can cross the compromised barrier (3,4). Although these tracer-based techniques provide valuable information about the status of BSCB, they are either fully invasive, necessitating histological analysis of tissue, or less invasive but still requiring intravenous injection of radio-tracers with subsequent blood sampling along with imaging, as in the case of autoradiography. Moreover, active transport mechanisms involved in some of these tracers may introduce a bias in quantifying the BSCB permeability (4).As an alternative to the above techniques, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with the exogenous paramagnetic contrast agent gadopentetate-dimeglumine (Gd, for short)...

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2-week-pregnant New Zealand White rabbits were placed into a hypobaric chamber and maintained at 3,657 m (12,000 ft). Upon delivery (31 ± 1 days) or at cesarean section (on day 30), all newborns were sacrificed and organ weights were compared to those of control pups maintained at 128 m (420 ft). Significant findings in the hypobaric animals included a diminished birth weight, placental weight, and liver weight per body weight. Placental weight per body weight was similar in both groups. The brain weight per body weight, brain to liver ratio, and right ventricle to left ventricle plus intraventricular septal weight ratio were significantly increased in the hypobaric pups.

The time dependence of N‐acetyl‐aspartate (NAA) concentrations relative to lactate and pyruvate in the injured rat spinal cord was investigated. Segments of spinal cord from regions rostral, caudal, and at the epicenter of the injury were analyzed. NAA concentrations were determined by gas chromatography‐mass spectrometry and lactate and pyruvate concentrations were determined by UV spectroscopy at 20 min, 60 min, 2 h, 8 h, 24 h, 3 days, and 1 week after injury. NAA levels fell most significantly at the epicenter of the injury, reaching 30% of basal levels within 24 h. In all segments, lactate levels increased significantly shortly after injury, peaking at two to five times normal basal levels between 20 and 60 min after injury. Rostral and caudal to the injury site, lactate elevations and NAA reductions were less dramatic. Pyruvate concentrations were not significantly altered in any of the sections after injury. The temporal and spatial relationships of NAA and lactate changes indicated that ischemic conditions due to injury in the upper thoracic rat spinal cord were distributed asymmetrically. Acute ischemia was more severe caudal to the injury site, and NAA concentrations were more severely impaired in the rostral direction. The results suggest that the extent of neuronal degeneration due to spinal cord injury does not correlate directly with acute ischemic severity as measured by the lactate/pyruvate ratio, and may be more closely related to secondary changes in the neuronal environment.

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Dissociated rat septal nucleus cells cultured in defined medium exhibited twofold increases in the maximal rates of sodium-dependent, high-affinity choline uptake and acetylcholine formation when grown in the presence of phosphoethanolamine. The effect was concentration-dependent (EC50 = 15 microM) and appeared to be associated with in vitro maturation of cholinergic neurons rather than with enhanced survival. Choline acetyltransferase, acetylcholinesterase, and choline kinase activities were unaffected by this treatment. The effect of phosphoethanolamine was specific for cholinergic neurons, because treatment with this compound did not alter the kinetic constants for high-affinity neuronal uptake of gamma-aminobutyric acid or dopamine. The action appeared to be mediated primarily through activation of the sodium-dependent, high-affinity transport mechanism for choline as opposed to alterations in the storage and release of acetylcholine.