Attenuation of decompressive hypoperfusion and cerebral edema by superoxide dismutase.

This study tested the hypothesis that ischemia-reperfusion injury initiated by the superoxide anion radical is a major component of postdecompression hypoperfusion and cerebral edema, and could be attenuated by superoxide dismutase (SOD). A supratentorial extradural balloon was placed in 20 fasting, lightly anesthetized, mechanically ventilated dogs and inflated in 0.5-ml increments (0.07 ml/sec) at 15-minute intervals. The end-point of balloon expansion was the onset of an isoelectric electroencephalogram, near-arrest of hemispheric cerebral blood flow (CBF) (measured by H2 clearance), and the appearance of a suprainfratentorial intracranial pressure gradient, which was held for 15 minutes. The in vivo development of brain edema was detected by measuring brain elastic response (BER) extradurally, and was correlated with postmortem measurement of brain water content (gravimetry); blood-brain barrier integrity was tested by Evans blue dye given after the insult. After decompression, the dogs were randomly assigned to one of four treatment groups: Group I received hyperventilation (PaCO2 28 +/- 1 mm Hg, mean +/- standard deviation); Group II received furosemide (2.4 mg/kg) and pentobarbital (10 mg/kg) every 8 hours; Group III received 20% mannitol in a 1.4-gm/kg bolus plus furosemide, 0.5 mg/kg; and Group IV received SOD, 15,000 U/kg every 15 minutes for 3 hours. At 4 hours of decompression Group IV had significantly greater recovery in local CBF and BER than Groups I, II, and III (p less than 0.05). The 24-hour survival rate was 20% for Group I, 60% for Group II, 80% for Group III, and 100% for Group IV. The survival rate appeared to correlate with a variable degree of postmortem intraparenchymal hemorrhages, blood-brain barrier disruption, and moderate to severe brain edema for Groups I, II, and III. In contrast, Group IV had the least brain edema (p less than 0.05) and Evans blue dye extravasation (p less than 0.05) and the fewest intraparenchymal hemorrhages. These data support the hypothesis that, under the experimental conditions described here, the superoxide anion plays a major role in the pathophysiology of postdecompression ischemic edema.

Anterior horn changes of motor neuron disease associated with demyelinating radiculopathy.

Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.