Striatal cholinergic interneuron numbers are increased in a rodent model of dystonic cerebral palsy.

Abstract

Neonatal brain injury leading to cerebral palsy (CP) is the most common cause of childhood dystonia, a painful and functionally debilitating movement disorder. Rare monogenic etiologies of dystonia have been associated with striatal cholinergic interneuron (ChI) pathology. However it is unclear whether striatal ChI pathology is also associated with dystonia following neonatal brain injury. We used unbiased stereology to estimate striatal ChI and parvalbumin-positive GABAergic interneuron (PVI) numbers in a rodent model of neonatal brain injury that demonstrates electrophysiological markers of dystonia and spasticity. Striatal ChI numbers are increased following neonatal brain injury while PVI numbers are unchanged. These numbers do not correlate with electrophysiologic measures of dystonia severity. This suggests that striatal ChI pathology, though present, may not be the primary pathophysiologic contributor to dystonia following neonatal brain injury. Increased striatal ChI numbers could instead represent a passenger or protective phenomenon in the setting of dystonic CP.