Loss of forebrain cholinergic neurons following fluid-percussion injury: implications for cognitive impairment in closed head injury.
Disturbances in memory, concentration, and problem solving are common after even mild to moderate traumatic brain injury. Because these functions are mediated in part by forebrain cholinergic and catecholaminergic innervation, in this study the authors sought to determine if experimental concussive injury produces detectable morphological damage to these systems. Fluid-percussion head injury, sufficient to cause a 13- to 14-minute loss of righting reflex, was produced in rats that had been anesthetized with halothane. Injury was delivered either at midline or 2 mm off midline and compared with appropriate sham-injured controls. After 11 to 15 days, the rat brains were stained in serial sections for choline acetyltransferase, tyrosine hydroxylase, dopamine beta-hydroxylase, acetylcholinesterase, and nicotinamide adenine dinucleotide phosphate diaphorase. Cell counts were determined for the entire population of ventrobasal forebrain cholinergic cells. Midline injury produced a bilateral loss of cholinergic neurons averaging 36% in area Ch1 (medial septal nucleus), 45% in Ch2 (nucleus of the diagonal band of Broca), and 41% in Ch4 (nucleus basalis of Meynart), (p < or = 0.05). Lateralized injury resulted in cholinergic neuron loss of similar magnitude ipsilaterally (p < or = 0.05), but a smaller contralateral loss of between 11% and 28%. No loss of neurons was detected in the pontomesencephalic cholinergic groups Ch5 and Ch6. There was no visible effect of head injury on forebrain dopamine or noradrenergic innervation. A significant and apparently selective loss of ventrobasal forebrain cholinergic neurons following brief concussive injury in rats is demonstrated in this study. This type of injury is known to produce significant disturbance in cognitive tasks linked to neocortical and hippocampal cholinergic function. It remains to be determined how this neuron loss occurs, whether it can be prevented with neuroprotective agents, how it affects innervation in target tissues, and whether it occurs in human victims of traumatic brain injury.
Schmidt
R H
RH
Department of Neurological Surgery, University of Washington, Seattle, USA.
Grady
M S
MS
D000320:Adrenergic Fibers / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology*; D002799:Cholinergic Fibers / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D006259:Craniocerebral Trauma / Q000150:complications*; D008297:Male; D016548:Prosencephalon / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014949:Wounds, Nonpenetrating / Q000150:complications