From laboratory to clinic: noradrenergic enhancement of physical therapy for stroke or trauma patients

Abstract

Research on treatments for cerebral stroke or traumatic brain injury (TBI) has focused on limiting the cascade of toxic pathologic events leading to primary and secondary neuronal death occurring early after injury. This approach of rescuing compromised neurons or "sparing" has had limited clinical success, and the very short therapeutic window limits therapeutic potential. This hopeless attitude for improving the status of patients weeks or a month after stroke may change with the accumulating data on the noradrenergic strategy. This approach uses any of a family of drugs to increase central levels of noradrenaline (NA), which, combined with physical therapy (NA/PT), produces an enduring alleviation of some symptoms of cortical injury. Importantly, beneficial effects of short-term treatment endure even when treatment is initiated a month after stroke. Long-term follow-up showed that the beneficial effect is robust, producing recovery to an ultimately higher level of hemiplegia recovery. Data from TBI patients indicate enhanced functional recovery of cognitive deficits using a similar intervention. The NA hypothesis for the beneficial effect is complemented with data from laboratory as well as from stroke patients that show slowing of recovery is produced by commonly prescribed drugs blocking alpha 1 NA receptors and other drugs shown harmful to recovery in animal models. Preliminary data suggest these beneficial and harmful effects on recovery may be extended to more complex functions such as aphasia. These findings are interpreted as NA modulation of a diaschisis, or remote functional depression in the cerebellum resulting from cortical injury.