The morphological and neurochemical effects of diffuse brain injury on rat central noradrenergic system.

The central noradrenergic system is widely distributed throughout the brain and is closely related to spontaneous motility and level of consciousness. The study presented here evaluated the morphological as well as neurochemical effects of diffuse brain injury on the central noradrenergic system in rat. Adult male Sprague-Dawley rats were subjected to impact-acceleration brain injury produced with a weight-drop device. Morphological changes in locus coeruleus (LC) neurons were examined by using immunohistochemistry for dopamine-beta-hydroxylase, and norepinephrine (NE) turnover in the cerebral cortex was measured by high performance liquid chromatography with electrochemical detection. The size of LC neurons increased by 11% 24 h after injury but had decreased by 27% seven days after injury. Axons of noradrenergic neurons were swollen 24 h and 48 h after injury but the swelling had dwindled in seven days. NE turnover was significantly reduced seven days after injury and remained at a low level until eight weeks after injury. These results suggest that focal impairment of axonal transport due to diffuse brain injury causes cellular changes in LC and that the neurochemical effect of injury on the central noradrenargic system lasts over an extended period of time. Chronic suppression of NE turnover may explain the sustained behavioral and psychological abnormalities observed in a clinical situation.