Enduring Vulnerability to Transient Reinstatement of Hemiplegia by Prazosin After Traumatic Brain Injury

Abstract

A single dose of an α₁-noradrenergic antagonist transiently reinstates hemiplegia after recovery from brain injury, which suggests that noradrenaline (NA) is required to maintain recovery. No systematic studies have determined the postinjury duration of this vulnerability. This study used a within-subject, dose-response design to determine whether prazosin (PRAZ), an α₁-NA antagonist, or propranolol (PROP), a β-NA antagonist, would continue to reinstate hemiplegia over time after recovery from weight-drop traumatic brain injury (TBI). PRAZ transiently reinstated hemiplegia as measured by beam walk (BW) score in a dose-dependent manner, with the same degree of symptom reinstatement at 1, 3, 6, and 12 months post-TBI. Between-animal variability in reinstatement of hemiplegia by PRAZ was predicted by severity of deficits in BW ability 24 h after TBI. In contrast, PRAZ did not reinstate tactile placing deficits at 1 month post-TBI suggesting a different mechanism of maintaining recovery for each task. Reinstatement of symptoms are not due to sedation. Only TBI rats receiving PRAZ, not high, sedating doses of PROP or saline (SAL), showed return of hemiplegia. These data indicate that vulnerability to transient reinstatement of hemiplegia on some tasks endures long after functional recovery from TBI.