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21 Aminosteroid

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Anders Holtz – 1st expert on this subject based on the ideXlab platform

  • effect of the 21 Aminosteroid u74006f and methylprednisolone on motor function recovery and oedema after spinal cord compression in rats
    Acta Neurologica Scandinavica, 2009
    Co-Authors: Mohammad Farooque, Yngve Olsson, Anders Holtz

    Abstract:

    : The effect of the 21Aminosteroid U74006F and methylprednisolone (MP) on motor function and oedema were investigated after spinal cord compression in rats. Each compound was administered i.v. as a single dose 60 min after injury. The hind limb motor function was assessed using the inclined plane technique and expressed as the capacity angle. The water content was calculated as the percent wet weight of the total weight. Prior to compression the capacity angle was close to 62-64 degrees. One day after compression the motor function was reduced significantly in all rats. However, the capacity angle was significantly higher after treatment with U74006F or MP than with vehicle, i.e. 50 degrees +/- 4, 45 degrees +/- 5, and 32 degrees +/- 3, respectively. This improved functional recovery persisted during the initial nine days. After compression of the spinal cord the water content increased to a maximum on day 4 in all groups. The water content was not significantly different in any of the groups except on day one and nine when it was less in groups treated with U74006F. In conclusion, a single i. v. injection of U74006 or MP given 60 min after compression of the spinal cord improved motor function without effecting oedema expressed as water content.

  • Effect of 21Aminosteroid on extracellular energy-related metabolites and amino acids after compression injury of rat spinal cord
    Experimental Brain Research, 1997
    Co-Authors: Mohammad Farooque, Yngve Olsson, Lars Hillered, Anders Holtz

    Abstract:

    We evaluated in a rat model of severe spinal cord compression the effect of the 21Aminosteroid tirilazad on extracellular levels of energy metabolites and amino acids, until 3 h after injury. The compound was given i.v. 30 min before injury (3 mg/kg) and hourly thereafter (1.5 mg/kg). The findings were compared with previously reported effects of methylprednisolone. Both treated and untreated rats with spinal cord compression showed, at 10 min after injury, a five-to sixfold elevation of extracellular lactate above the preinjury level. There was no significant difference for lactate, pyruvate or lactate/pyruvate ratio between the treated and untreated injured groups at any time point after trauma. Glutamate was significantly elevated both in treated and untreated injured rats for 20 min after trauma. The mean glutamate level was lower in animals treated with 21Aminosteroid. However, there was no statistically significant difference between the treated and untreated rats at any time after trauma. There was no statistically significant difference between the groups for aspartate, serine, glutamine, histidine, glycine, threonine, taurine, alanine and tyrosine. In conclusion our findings indicate that, in the injured spinal cord, methylprednisolone and the 21Aminosteroid have differences and similarities, regarding their effects on energy and amino acid metabolism. The lowering of the lactate and arginine levels early after trauma seen with methylprednisolone pretreatment was absent after 21Aminosteroid pretreatment. However, the mean extracellular level of glutamate was lower with both methyl-prednisolone and 21Aminosteroid after injury, although the difference was not statistically significant between treated and untreated rats.

  • efficacy of the 21 Aminosteroid u74006f in improving neurological recovery after spinal cord injury in rats
    Neurological Research, 1992
    Co-Authors: Anders Holtz, Bengt Gerdin

    Abstract:

    AbstractThe efficacy of three different regimens of the 21Aminosteroid U74006F in counteracting the neurological damage after spinal cord compression causing paraparesis in rats was investigated. Three groups of ten animals each were given totally 6 mg I kg of U74006F in different regimens beginning one hour after injury (A: bolus doses of 1.5 mg/kg at 1, 4, 7 and 10 hours; B: bolus of 1.5 mg/kg at 1 hour and 4.5 mg/kg as an infusion over the next 9 hours; and C: infusion alone, 6 mg/kg, given between 1 and 10 hours after trauma). Two groups of ten animals each received vehicle alone in administration modes comparable to those of the U74006F treated animals. The motor function was assessed daily on the inclined plane. On day one, the capacity angle had decreased from about 62 ° preoperatively to 28-30 ° in the two vehicle-treated groups and in group C. In these groups there was a similar improvement in neurological function and on day 9 the capacity angles were 49-55 °. In groups A and B, both of which r…

Michael Banbury – 2nd expert on this subject based on the ideXlab platform

  • The novel 21Aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat.
    Journal of Neurotrauma, 1992
    Co-Authors: Tracy K Mcintosh, Mark G Thomas, Douglas H Smith, Michael Banbury

    Abstract:

    The present study evaluated the effect of the nonglucocorticoid 21Aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21Aminosteroids may be beneficial in the treatment of brain injury.

  • the novel 21 Aminosteroid u74006f attenuates cerebral edema and improves survival after brain injury in the rat
    Journal of Neurotrauma, 1992
    Co-Authors: Tracy K Mcintosh, Mark G Thomas, Douglas H Smith, Michael Banbury

    Abstract:

    The present study evaluated the effect of the non-glucocorticoid 21Aminosteroid U74006F on the development of regional cerebral oedema after lateral fluid-percussion (FP) brain injury in the rat. Male Sprague-Dawley rats (n = 20) were anaesthetized and subjected to lateral FP brain injury of moderate severity (2.5–2.6 atmospheres). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 11) followed by a second bolus (3 mg/kg) at 3 hours vs buffered saline vehicle (equal volume, n = 9). At 48 hours postinjury, animals were sacrificed and brains tissue assayed for water content using wet weight/dry weight methodology. Administration of U74006F significantly attenuated the increase in water content observed in control animals in the ipsilateral hippocampus (adjacent to the site of maximal injury, p < 0.05). Administration of U74006F also significantly reduced post-injury mortality from 28% in control animals to zero in treated animals (p < 0.001). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21Aminosteroids may be beneficial in the treatment of brain injury.

  • the novel 21 Aminosteroid u 74006f attenuates cerebral oedema and improves survival after brain injury in the rat
    Acta Neurochirurgica, 1990
    Co-Authors: Tracy K Mcintosh, Michael Banbury, Douglas H Smith, Mark G Thomas

    Abstract:

    : The present study evaluated the effect of the non-glucocorticoid 21Aminosteroid U74006F on the development of regional cerebral oedema after lateral fluid-percussion (FP) brain injury in the rat. Male Sprague-Dawley rats (n = 20) were anaesthetized and subjected to lateral FP brain injury of moderate severity (2.5-2.6 atmospheres). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 11) followed by a second bolus (3 mg/kg) at 3 hours vs buffered saline vehicle (equal volume, n = 9). At 48 hours postinjury, animals were sacrificed and brains tissue assayed for water content using wet weight/dry weight methodology. Administration of U74006F significantly attenuated the increase in water content observed in control animals in the ipsilateral hippocampus (adjacent to the site of maximal injury, p less than 0.05). Administration of U74006F also significantly reduced post-injury mortality from 28% in control animals to zero in treated animals (p less than 0.001). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21Aminosteroids may be beneficial in the treatment of brain injury.

Edward D Hall – 3rd expert on this subject based on the ideXlab platform

  • attenuation of motor nerve terminal repetitive discharge by the 21 Aminosteroid tirilazad evidence of a neural calcium antagonist action
    Brain Research, 1998
    Co-Authors: Edward D Hall, Patricia A Yonkers

    Abstract:

    Abstract Pretreatment with the 21Aminosteroid antioxidant compound tirilazad mesylate has been previously shown to retard the axotomy-induced anterograde degeneration of soleus motor nerve terminals in the cat. In the present study, we examined tirilazad’s effects (7.7, 13.0 or 30.0 mg/kg twice daily P.O. for 6 days) on the excitability of normal cat soleus motor nerve terminals. Low frequency (0.4 Hz) neuromuscular transmission was measured as well as the occurrence of muscle contractile potentiation in response to either a 400 Hz/10 s episode of tetanic conditioning stimulation of the soleus nerve or the administration of a 200 μg/kg i.v. dose of the neuromuscular facilitatory drug edrophonium. The mechanism of the post-tetanic potentiation (PTP) or edrophonium-induced facilitatory response involves the occurrence of a stimulus-dependent repetitive discharge of the soleus motor nerve terminals due to an exaggeration of the nerve terminal Ca2+-mediated after-depolarization. Tirilazad pretreatment caused a dose-related suppression of PTP and the edrophonium response indicative of a suppression of motor nerve terminal repetitive discharge. These effects were not shared by 6 days of oral pretreatment of cats with a high dose combination of the antioxidants vitamin E (200 I.U./day) and selenium (50 μg/day). Thus, it is unlikely that the antioxidant properties of tirilazad are involved in the suppression of motor nerve terminal excitability. Rather, it is proposed that tirilazad suppresses delayed motor nerve terminal Ca2+ conductances secondary to its ability to decrease membrane phospholipid fluidity, and that this action might in some circumstances contribute to its neuroprotective activity.

  • therapeutic value of 21 Aminosteroid u74389f in acute spinal cord injury
    Neurological Research, 1993
    Co-Authors: Siavash S. Haghighi, Edward D Hall, Xiao Z Geng, Gayle C Johnson

    Abstract:

    AbstractThe effect of bolus injections of 21Aminosteroid U74389F after an acute spinal cord compression trauma in rats was studied. Cortical somatosensory evoked potentials (CSEPs) were recorded before and after a weight-induced injury of 120 g and monitored up to five hours post-injury. All U74389F treatments were given as i.v. bolus injections of 15, 7.5, and 3.75 mg kg–1 at 1, 2, 3 h after the trauma, respectively. The CSEPs were abolished immediately after the injury in the control and treated animals. The majority of the treated animals (88.8%) demonstrated a return of the CSEPs within the second hour post-injury. In contrast, the animals in the control group showed only 44.4% recovery at this time period. At three hours post-injury, U74389F-treated animals (n = 18) showed a full recovery (100%) while the recovery rate remained at 44.4% for the control animals. We conclude that the bolus administration of U74389F one hour after injury facilitates the return of the spinal cord function as measured by…

  • Therapeutic value of 21Aminosteroid U74389F in acute spinal cord injury.
    Neurological Research, 1993
    Co-Authors: Siavash S. Haghighi, Edward D Hall, Xiao Z Geng, Gayle C Johnson

    Abstract:

    The effect of bolus injections of 21Aminosteroid U74389F after an acute spinal cord compression trauma in rats was studied. Cortical somatosensory evoked potentials (CSEPs) were recorded before and after a weight-induced injury of 120 g and monitored up to five hours post-injury. All U74389F treatments were given as i.v. bolus injections of 15, 7.5, and 3.75 mg kg-1 at 1, 2, 3 h after the trauma, respectively. The CSEPs were abolished immediately after the injury in the control and treated animals. The majority of the treated animals (88.8%) demonstrated a return of the CSEPs within the second hour post-injury. In contrast, the animals in the control group showed only 44.4% recovery at this time period. At three hours post-injury, U74389F-treated animals (n = 18) showed a full recovery (100%) while the recovery rate remained at 44.4% for the control animals. We conclude that the bolus administration of U74389F one hour after injury facilitates the return of the spinal cord function as measured by the CSEPs in this compression model of acute spinal cord trauma.