Gender-related differences in recovery of locomotor function after spinal cord injury in mice.

STUDY DESIGN: In order to study the role of gender in recovery, we induced a thoracic compression spinal cord injury (SCI) separately in 2-month-old male and female C57Bl/6 mice. OBJECTIVES: We intended to assess effects of gender on recovery of hindlimb motor function and to correlate these with histomorphologic profiles of injured spinal cord tissue. METHODS: Locomotor function was evaluated by three means: a modified locomotor scoring system for rodents, beam walking and computerized activity meter. Histology was analyzed by comparison of hematoxylin and eosin-stained perfused specimens. RESULTS: Locomotor scores were 2.2+/-0.9 on day 1 in male mice, while, in contrast, they were significantly higher, 7.3+/-1.7, in females (P<0.02). On day 14 Basso, Beattie and Bresnahan scores were 9.5+/-2.2 in male mice and 16.0+/-2.2 in females (P<0.03). Terminal histology showed that the spinal cord architecture was relatively better preserved in female mice and that the extent of necrosis and infiltration of inflammatory cells was less compared to males. SETTING: Neurobiology Research Laboratory of University of Kansas Medical School in US Department of Veterans Affairs Medical Center, Kansas City, Missouri. CONCLUSION: We found that the severity of the initial injury as well as the ultimate recovery of motor function after SCI is significantly influenced by gender, being remarkably better in females. The mechanism(s) of neuroprotection in females, although not yet elucidated, may be associated with the effects of estrogen on pathophysiological processes (blood flow, leukocyte migration inhibition, antioxidant properties, and inhibition of apoptosis). SPONSORSHIP: Medical Research, US Department of Veterans Affairs, the Christopher Reeve Paralysis Foundation and NIH.

Ferritin, transferrin and iron concentrations in the cerebrospinal fluid of multiple sclerosis patients.

The concentrations of ferritin, transferrin and iron were measured in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) and control patients. Ferritin levels were significantly elevated in the CSF of chronic progressive active MS patients (4.71+/-0.54 ng/ml) compared to levels in normal individuals (3.07+/-0.17 ng/ml). MS patients with active or stable relapsing-remitting disease had ferritin levels that were comparable to those found in normal individuals. There were no significant differences in transferrin or iron levels in the CSF between MS and normal individuals. Both ferritin and transferrin levels were elevated in patients that had high CSF IgG values but not in patients with a high IgG index. Since ferritin binds iron, the increase of CSF ferritin levels in chronic progressive MS patients could be a defense mechanism to protect against iron induced oxidative injury. Ferritin levels could be a laboratory measure that helps to distinguish between chronic progressive and relapsing-remitting MS.

Iron quantification in cerebrospinal fluid.

Several studies have attempted to measure iron levels in cerebrospinal fluid (CSF), which is believed to contain very low levels of iron. In general, the assays used in these studies suffered from poor reproducibility or lack of sensitivity. In the present study, an assay was developed that enables iron quantitation in CSF using 150 microliters of undiluted CSF, sample digestion, dot blotting, Perls' histochemistry, 3,3'-diaminobenzidine enhancement, and densitometry. Inter- and intraassay variability was low and sensitivity high (279 pg iron in 100 microliters). There were negligible readings for standard curves utilizing copper in place of iron. The iron content in eight normal CSF samples was 61.01 +/- 18.3 (SD) micrograms/liter, and in nine normal sera it was 1332.7 +/- 408.2 (SD) micrograms/liter. The present assay enables reliable measures of iron levels in biological samples. This assay should enable future studies that address how CSF iron levels change during the course of various disease states.

Ovulatory delay alters postnatal growth, behavior, and brain structure in rats.

To investigate the effect of a delay in ovulation on postnatal growth and development in resultant rat offspring, a 1-day ovulatory delay was induced by sodium pentobarbital, animals mated, and the offspring monitored. There were no differences between control and 1-day delayed offspring in the number of live or dead births, number of males or females, nor in the ratio of sexes. Delayed pups had a slightly lower birth weight, but then recovered to weigh more than controls by day 12. In the first two weeks post-parturition, delayed pups displayed an earlier ability to reorient themselves in a negative geotaxis test, but no differences by the righting reflex and reflex suspension tests. At postnatal day (pnd) 28, delayed pups exhibited decreased activity in a continuous corridor test, but no alterations in gait. At this time, the brains of delayed animals revealed thickening of cortical layers V plus VI. There were significant correlations between various developmental endpoints (body weight, negative geotaxis, continuous corridor activity, and gait) and the cortical layer thicknesses. The results indicate that ovulatory delay produces changes in brain cortical thickness, with correlative changes in growth and behavior. Although the mechanisms by which ovulatory delay alters postnatal development and brain structure are unknown, ovulatory delay may alter the uterine environment during early pregnancy.