Quantitative morphological analysis of striatal cholinergic neurons in perinatal asphyxia

Although the static encephalopathies of childhood are common, little is known of the underlying alterations in the neurochemical anatomy of the brain. Using quantitative morphological techniques, we examined the effect of perinatal hypoxia-ischemia on the number and distribution of cholinergic (ACh) neurons in a unilateral experimental striatal lesion in rats. The striatal pathology simulates status marmoratus, a recognized correlate of human dystonic cerebral palsy. We found that striatal injury results in a mean 22% decrease in the number of ACh neurons at the age of 3 to 4 weeks. The loss of neurons was relatively less than the volume loss, resulting in a mean 16% increase in neuron density. This effect was not uniform throughout the striatum; it was more pronounced caudally, resulting in a mean 52% increase in density in the most caudal striatal plane. These changes in immature rats were also seen in adult rats, indicating that there were lasting alterations in striatal cholinergic morphology. Hypoxic-ischemic injury to the striatum also resulted in a persistent decrease in the mean area of ACh neurons. The increased density of these neurons may imply that they are relatively resistant to hypoxic-ischemic injury. These findings may be relevant to the observation that anticholinergic drugs are among the most effective for treating dystonias, including those observed in static encephalopathies.