iloprost and Spinal-Cord-Injuries

The thoracic or thoracoabdominal aortic aneurysm surgery may cause spinal cord ischemia because of aortic cross-clamping and may result in severe postoperative complications caused by spinal cord injury. Ischemia/reperfusion injury may directly or indirectly be responsible for these complications. In this study we sought to determine whether combination of iloprost and montelukast can reduce the ischemia/reperfusion injury of spinal cord in a rat model.. Medulla spinalis tissue concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO) and heat shock protein 70 (HSP-70) were determined in 3 groups of Spraque Dawley rats: control group (operation with cross clamping and intraperitoneal administration of 0.9% saline, n = 7), sham group (operation without cross clamping, n = 7), and study group (operation with cross-clamping and intraperitoneal administration of iloprost (25 ng/kg) and montelukast (1 mg/kg), n = 7). The abdominal aorta was clamped for 45 minutes, with a proximal (just below the left renal artery) and a distal (just above the aortic bifurcation) clip in control and study groups. Hindlimb motor functions were evaluated at 6, 12, 24, and 48 hours using the Motor Deficit Index score. All rats were sacrificed 48 hours after the procedure and spinal cord tissue levels of myeloperoxidase, interleukin-6, and heat shock protein (HSP-70) were evaluated as markers of oxidative stress and inflammation. Histopathological analyses of spinal cord were also performed.. The tissue level of HSP-70 was found to be similar among the 3 groups, however, MPO was highest and IL-6 receptor level was lowest in the control group (p = 0.007 and p = 0.005; respectively). In histopathological examination, there was no significant difference among the groups with respect to the neuronal cell degeneration, edema, or inflammation, but vascular congestion was found to be significantly more prominent in the control group than in the sham or in the study group (p = 0.05). Motor deficit index scores at 24 and 48 hours after ischemia were significantly lower in the study group than in the control group.. This study suggests that combined use of iloprost and montelukast may reduce ischemic damage in transient spinal cord ischemia and may provide better neurological outcome.

Topics: Acetates; Animals; Biomarkers; Cyclopropanes; Drug Administration Schedule; Drug Therapy, Combination; Iloprost; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxidative Stress; Quinolines; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord; Spinal Cord Injuries; Sulfides; Treatment Outcome

We investigated the role of prostacyclin (PGI(2)) in the development of compression trauma-induced spinal cord injury (SCI) in rats. When measured after induction of SCI, tissue levels of 6-keto-PGF(1), a stable PGI(2) metabolite, thromboxane B(2) (TXB(2)), a stable metabolite of thromboxane A(2), myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF) in the injured spinal cord segment were significantly increased, peaking at 2, 3, and 4 h after induction of SCI, respectively. Subcutaneous administration of indomethacin (IM), a non-selective cyclooxygenase (COX) inhibitor, completely inhibited increases in tissue levels of 6-keto-PGF(1) and TXB(2), while administration of NS-398, a selective inhibitor of COX-2, did not affect these increases. Although pretreatment with IM enhanced increases in tissue levels of MPO, TNF, and TNF mRNA and exacerbated both motor disturbances and histological damage in the spinal cord of animals subjected to SCI, pretreatment with NS-398 had no effect on any of these findings. Both iloprost, a stable analog of PGI(2), and leukocyte depletion significantly reversed changes in various variables and exacerbation of motor disturbances induced by IM pretreatment in animals subjected to SCI. These observations strongly suggested that compression trauma-induced increase in PGI(2) production in spinal cord tissue might be mainly mediated by COX-1 and PGI(2) might play a critical role in reduction of motor disturbances following SCI by inhibiting neutrophil accumulation through inhibition of TNF production.

Topics: Animals; Cyclooxygenase Inhibitors; Epoprostenol; Iloprost; Indomethacin; Male; Motor Activity; Neutrophil Infiltration; Nitrobenzenes; Rats; Rats, Wistar; RNA, Messenger; Spinal Cord Injuries; Sulfonamides; Thoracic Vertebrae; Tumor Necrosis Factor-alpha

It has been increasingly reported that traumatic and ischemic insults to the spinal cord may produce tissue damage through both direct and indirect mechanisms. In spite of many theories about post-traumatic spinal cord injury, there is still no satisfactory account of the exact mechanism. Vasospasm may be related to the trauma and release of vasoconstrictor or vasoactive amines. This study aims at studying the possible protective mechanisms of iloprost, a stable analogue of prostacyclin, after spinal cord injury on the rabbit. Forty-two adult male rabbits (New Zealand albino) were inflicted injuries by epidural application of an aneurysm clip to the spinal cord. Twenty-one rabbits received an i.v. infusion of 25 microg kg(-1) x h(-1) iloprost. The remaining twenty-one rabbits received an i.v. infusion of saline as the control group. Intravenous treatment started immediately after the infliction of the spinal cord injury and lasted for 1 h. Iloprost treatment had no side effects on the general physiological parameters in the rabbits. Control and iloprost treatment groups were divided into three sub-groups. The first group of animals was deeply anesthetized and spinal cords were removed 15 min after treatment. Second and third group animals were sacrificed in the 3rd and 24th hours respectively. All spinal cords were removed for light and electron microscopic examination. The width of anteriolar smooth muscle cells and the ultrastructural analysis of sulcal arterioles and venules in the ventral median fissure of spinal cords treated by iloprost revealed less thickening in all groups especially on the 24th hour group (p < 0.01), but less thickening was observed on the 3rd hour group. Iloprost-treated groups had limited edema and moderate protection of myelin and axons. These results suggest that iloprost treatment after spinal cord injury has a highly protective effect, and the possible protective effect of iloprost is resolution of vasospasm due to spinal cord injury.

Topics: Animals; Arterioles; Iloprost; Male; Microscopy, Electron; Nerve Fibers, Myelinated; Rabbits; Spinal Cord; Spinal Cord Injuries; Vasodilator Agents; Vasospasm, Intracranial; Venules

This investigation was undertaken to study the early protective effects of Iloprost, a stable analogue of prostacyclin, after spinal cord injury in rabbit. Sixteen adult male rabbits (New Zealand Albino) were injured by application of epidural aneurysm clip. Eight rabbits received an intravenous (i.v.) infusion of 30 micrograms kg-1 Iloprost, and eight rabbits received an infusion of saline (SF). Treatment with Iloprost started immediately after spinal cord injury and continued for one hour. Evoked potentials were recorded for each rabbit at one, 15, and 60 minutes after the spinal cord injury. Twenty-four hours later, all the rabbits were deeply anesthetized and spinal cords were removed for histopathological examinations. There was no meaningful statistical difference between cortical somatosensorial evoked potentials (CSEP) of the saline and Iloprost group. However, light and electron microscopic studies showed that the Iloprost treated group had moderate protection of myelin and axons; and limited edema. These results suggest that intravenous Iloprost treatment after spinal cord injury has a highly protective effect without any side effects.

Topics: Animals; Brain Edema; Evoked Potentials, Somatosensory; Iloprost; Male; Microscopy, Electron; Rabbits; Spinal Cord Injuries; Vasodilator Agents

To investigate whether iloprost, a stable analog of prostacyclin, is useful for the prevention of posttraumatic spinal cord injury, we examined its effects on compression trauma-induced spinal cord injury in rats. Spinal cord injury was induced by applying a 20-g weight for 20 minutes to the spinal cord at the level of T-12, resulting in motor disturbances in the hindlimbs. These motor disturbances, evaluated using Tarlov's index, were markedly attenuated in rats with nitrogen mustard-induced leukocytopenia. Administration of iloprost also attenuated the motor deficits. Histological examination revealed that intramedullary hemorrhages observed 24 hours after trauma were significantly attenuated in leukocytopenic animals and in animals that received iloprost. The accumulation of leukocytes at the site of trauma, evaluated by measuring tissue myeloperoxidase activity, significantly increased with time following the trauma, peaking at 3 hours postinjury. Spinal cord myeloperoxidase activity in sham-operated animals did not increase postoperatively. Leukocyte depletion and administration of iloprost reduced the accumulation of leukocytes in the damaged spinal cord segment 3 hours posttrauma. These findings indicate that iloprost attenuates motor disturbances induced by spinal cord trauma and that its therapeutic efficacy can be partly explained by its inhibition of leukocyte accumulation at the traumatized site.

Topics: Animals; Epoprostenol; Iloprost; Leukopenia; Male; Mechlorethamine; Peroxidase; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Wounds, Nonpenetrating