The effect of an alpha-2 agonist on bladder function and cord histology after spinal cord injury.

Spinal injury in cats is accompanied by urinary bladder and hind limb dysfunction. Ten cats subjected to spinal contusion at the ninth thoracic segment were treated with guanabenz (an alpha-2 agonist) intraperitoneally (0.65 mg./kg.) three hours after injury, and twice daily for eight weeks. An additional six spinal cats were untreated and served as controls. Urodynamic studies were performed on a weekly basis on all animals. Guanabenz modified the vesico-somatic reflex: detrusor-sphincter dyssynergia was either ablated or abolished. In contrast, the controls demonstrated detrusor-sphincter dyssynergia, high residual urine, and spasticity below the lesion. Histological evaluations of the spinal cords revealed that the six paraplegic animals (untreated) suffered marked cavitation of the cord and complete destruction of the grey matter. The five incomplete paraplegic animals (treated) showed minimal cavitation with some preservation of the grey matter. The five ambulators (treated) demonstrated some distortion of grey matter with preservation of white matter. Treatment with guanabenz post traumatic cord injury results in decreased cord cavitation. Detrusor-sphincter dyssynergia is diminished and hind limb function is improved in treated animals.

Ascorbic acid: a putative biochemical marker of irreversible neurologic functional loss following spinal cord injury.

The development of permanent paraplegia in spinal injured cats is accompanied by a large progressive decline in total ascorbic acid (AA) and a transient increase in oxidized (AAox) ascorbate. Since AA is involved in a variety of processes required for normal central nervous system (CNS) performance we suggested that such large ascorbate loss may contribute to derangements in spinal cord function following injury. We now demonstrate that methylprednisolone (15 mg/kg) and naloxone (10 mg/kg), two treatments that preserve neurologic function in this model, rapidly block deteriorating ascorbate status. Naloxone at 1 mg/kg, a treatment providing no therapeutic benefit, has no protective effect on ascorbate. The results strongly support the hypothesis that loss of ascorbate homeostasis reflects irreversible loss of neurologic function following spinal cord injury.

Experimental spinal cord injury: treatment with naloxone.

We studied the effect of the opiate antagonist naloxone on the recovery of cats injured with a 400-g-cm impact injury to T-9. The animals were evaluated by recording somatosensory evoked potentials and performing weekly neurological examinations. Several dose schedules were followed. Six of eight cats that received an intravenous or intraperitoneal bolus of naloxone (10 mg/kg) 45 minutes after injury regained the ability to walk. Recovery occurred in only one of five animals that were treated with an infusion of naloxone, 10 mg/kg/hour, and in none of five animals given 1 mg/kg as a bolus. Because these results are not related to any observed change in blood pressure, we believe that naloxone may be achieving its effect through the preservation of spinal cord blood flow, as well as other mechanisms that have yet to be defined.

Effect of naloxone on posttraumatic ischemia in experimental spinal contusion.

The effect of naloxone on blood flow and somatosensory evoked potentials was studied in cats subjected to 400 gm-cm contusion injuries of the thoracic spinal cord. Eight cats were treated with 10 mg/kg naloxone 45 to 60 minutes after injury, 11 cats were given 10 ml of saline instead of naloxone, and six cats were neither injured nor treated. Hydrogen clearance was used to measure blood flow in the lateral white columns at the contusion site. Naloxone, given intravenously, significantly inproved the blood flow rates in the lateral column white matter. At 2 hours after injury, the mean blood flow in the saline-treated cats fell to 50% (p greater than 0.01) of preinjury flow rates, whereas it increased 6% (p greater than 0.50) in naloxone-treated cats, and 12% (p greater than 0.50) in uninjured cats. At the 3rd hour after injury, the respective flows fell 47% (p less than 0.01), and 6% (p greater than 0.50), and increased 15% (p greater than 0.50) of the preinjury flow rates. The naloxone-treated cats had striking preservation of sensory function and somatosensory evoked potentials at 24 hours after injury. At 24 hours, responses had returned in all the naloxone-treated cats and in only 11% of the saline-treated cats. The probability of this combination of events occurring by chance is 0.0030. The authors conclude that naloxone may be useful for the treatment of spinal cord injury. The mechanism of the effect is unknown.

Effect of aminophylline and isoproterenol on spinal cord blood flow after impact injury.

A study of the effects of spinal cord injury upon spinal cord blood flow was carried out in cats. A 400 mg-cm impact produced an overall reduction in spinal cord blood flow of 24% in the white matter and 30% in the gray matter, as determined by 14C-antipyrine autoradiography. At the level of the injury, white-matter flow was 8.1 ml/100 gm/min, a reduction of 49%, and in the gray matter, 12.5 ml/100 gm/min, a reduction of 76%. Treatment with aminophylline and isoproterenol improved the overall blood flow in the spinal cord. At the level of the injury, white-matter flow after this treatment was no longer significantly different from control values. The gray-matter flow remained decreased to 26.2 ml/100 gm/min, a reduction of only 47%. It is proposed that aminophylline and isoproterenol may increase cyclic adenosine monophosphate (AMP) and prevent platelet aggregation along the endothelial surfaces of the microcirculation, and may thereby help to maintain improved perfusion of the injured spinal cord.

The role of the sympathetic nervous system in pressor responses induced by spinal injury.

Spinal cord injury consistently evokes a transient 3- to 4-minute rise is systemic pressure, followed by prolonged hypotension. Because the role of the sympathetic nervous system in these blood pressure changes is not clear, the pressure responses were studied using systematic ablation of the peripheral sympathetic nervous system. In total, 24 cats were subjected to bilateral thoracic sympathectomy, adrenalectomy, splanchnicectomy, combinations of the preceding, sham operation, or no treatment. Either 3 or 24 hours after the ablations, the blood pressure responses were evoked by 400 gm-cm contusions of the thoracic cord. Although neither thoracic sympathectomy nor adrenalectomy alone abolished the hypertensive phase, the combination of the two procedures did. This suggests that both the thoracic sympathetic ganglia and the adrenal glands participate in the pressor response. Thoracic sympathectomy affected primarily the early part, whereas adrenalectomy diminished the later part of the hypertensive response. This correlates with the function of the former being neurally and the latter being humorally mediated. None of the sympathetic lesions consistently affected the hypotensive phase. Spinal contusion injury produces widespread sympathetic activation, mediating the hypertensive changes.

Ethanol potentiation of central nervous system trauma.

Two models have been used to study the effects of ethanol on injuries of the central nervous system. The spinal cords of cats were injured by delivering a 200 gm-cm impact to the exposed dura mater. A second group of animals received a similar injury to the exposed dura mater overlying the cerebral hemispheres. The animals were divided into two groups, those that received an infusion of ethanol before injury, and control animals that received no ethanol. The parameters of injury used in this model produced small and insignificant lesions in those animals that received no ethanol; however, when the animals were pretreated with ethanol, a considerable increase in the extent of the injury was noted. These include alterations in membranes-bound enzymes and clotting mechanisms, and alteration of cell membranes through abnormal free radical reactions.