Journal of neurotrauma
-
Journal of neurotrauma · Jun 2006
17beta-estradiol is protective in spinal cord injury in post- and pre-menopausal rats.
The neuroprotective effects of 17 beta -estradiol have been shown in models of central nervous system injury, including ischemia, brain injury, and more recently, spinal cord injury (SCI). Recent epidemiological trends suggest that SCIs in elderly women are increasing; however, the effects of menopause on estrogen-mediated neuroprotection are poorly understood. The objective of this study was to evaluate the effects of 17beta-estradiol and reproductive aging on motor function, neuronal death, and white matter sparing after SCI of post- and pre-menopausal rats. ⋯ Administration of 17beta-estradiol to ovariectomized rats improved recovery of hind-limb locomotion, increased white matter sparing, and decreased apoptosis in both the post- and pre-menopausal rats. Also, ovary-intact 1-year-old rats did worse than ovary-intact 2-month-old rats, suggesting that endogenous estrogen confers neuroprotection in young rats, which is lost in older animals. Taken together, these data suggest that estrogen is neuroprotective in SCI and that the loss of endogenous estrogen-mediated neuroprotective seen in older rats can be attenuated with exogenous administration of 17beta-estradiol.
-
Journal of neurotrauma · May 2006
Comparative StudyBasso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.
Genetically engineered mice are used extensively to examine molecular responses to spinal cord injury (SCI). Inherent strain differences may confound behavioral outcomes; therefore, behavioral characterization of several strains after SCI is warranted. The Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) for rats has been widely used for SCI mice, but may not accurately reflect their unique recovery pattern. ⋯ BMS revealed significantly higher recovery in C57BL/10, B10. PL and F1 than the C57BL/6 and BALB/c strains after moderate SCI (p < 0.05). The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.
-
Journal of neurotrauma · May 2006
Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats.
Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system. Numerous studies have shown its neuroprotective effects both in vitro and in vivo. Previously, it has been demonstrated that PACAP reduces brain damage in rat models of global and focal cerebral ischemia. ⋯ There was no significant difference between the density of beta-APP-immunopositive axons in the medial longitudinal fascicle (MLF). PACAP treatment did not result in significantly different number of RMO-14-immunopositive axonal profiles in either brain areas 2 hours post-injury compared to normal animals. While the results of this study highlighted the complexity of the pathogenesis and manifestation of diffuse axonal injury, they also indicate that PACAP should be considered a potential therapeutic agent in TBI.
-
Journal of neurotrauma · May 2006
Early morphologic and spectroscopic magnetic resonance in severe traumatic brain injuries can detect "invisible brain stem damage" and predict "vegetative states".
A precise evaluation of the brain damage in the first days of severe traumatic brain injured (TBI) patients is still uncertain despite numerous available cerebral evaluation methods and imaging. In 5-10% of severe TBI patients, clinicians remain concerned with prolonged coma and long-term marked cognitive impairment unexplained by normal morphological T2 star, flair, and diffusion magnetic resonance imaging (MRI). For this reason, we prospectively assessed the potential value of magnetic resonance spectroscopy (MRS) of the brain stem to evaluate the functionality of the consciousness areas. ⋯ However, a principal component analysis of combined MRI and MRS data enabled a clear-cut separation between GOS 1-2, GOS 3, and GOS 4-5 patients with no overlap between groups. This study showed that combined MRI and MRS provide a reliable evaluation of patients presenting in deep coma, specially when there are insufficient MRI lesions of the consciousness pathways to explain their status. In the first few days post-trauma metabolic (brainstem spectroscopy) and morphological (T2 star and Flair) MRI studies can predict the long-term neurological outcome, especially the persistent vegetative states and minimally conscious state.
-
Journal of neurotrauma · May 2006
Inhibition of Fas-mediated apoptosis through administration of soluble Fas receptor improves functional outcome and reduces posttraumatic axonal degeneration after acute spinal cord injury.
Fas receptor activation has been implicated in inflammatory responses, programmed cell death, Wallerian degeneration in neural injury and the axotomy induced death of motoneurons. Recent work using transection models of spinal cord injury (SCI) demonstrated that neutralization of Fas ligand with antibodies may promote axonal regeneration and functional recovery. Moreover, recent studies from our laboratory in mutant mice with deficient expression of Fas, show reduced cell death and enhanced behavioural recovery after SCI. ⋯ An in vitro model of SCI demonstrated that sFasR administration decreases cell death as assessed by propidium iodide fluorescence. Furthermore, in a moderately severe in vivo clip compression model of SCI at C7-T1, we demonstrate that subarachnoid infusion of sFasR results in increased neuron and oligodendrocyte survival, improved tissue and long tract axonal preservation, reduced apoptotic cell death and enhanced functional neurological outcome after acute SCI. These results strongly suggest that inhibiting Fas receptor activation is neuroprotective after acute SCI and that this strategy may have important translational significance.