Cortical cholinergic dysfunction after human head injury.
Loss of cholinergic neurotransmission is implicated in memory impairment and cognitive dysfunction after head injury. The aim of the present study was to investigate presynaptic markers, particularly in relation to cholinergic neurotransmission in human postmortem brain from patients who died following a head injury and age-matched controls. Choline acetyltransferase activity and high-affinity nicotinic receptor binding sites were assayed in the inferior temporal gyrus, cingulate gyrus, and superior parietal cortex of 16 head-injured patients and 8 controls. Synaptophysin immunoreactivity was determined in the left cingulate gyrus from the same patient groups. In the head-injured group, choline acetyltransferase activity was consistently reduced in each cortical region compared to control subjects. The presence of a subdural haematoma and a prolonged survival period after head injury tended to be associated with lower choline acetyltransferase activity. In contrast to the marked reduction in choline acetyltransferase activity, nicotine receptor binding was unchanged in head-injured compared to control patients. Synaptophysin immunoreactivity in the cingulate gyrus was reduced by approximately 30% (p < 0.05) in the head-injured group compared to controls. Correlation of choline acetyltransferase activity with synaptophysin immunoreactivity indicated there is a deficit of cholinergic presynaptic terminals in postmortem human brain following head injury.
Murdoch
I
I
Wellcome Surgical Institute & Hugh Fraser Neuroscience Laboratories, University of Glasgow, United Kingdom.
Perry
E K
EK
Court
J A
JA
Graham
D I
DI
Dewar
D
D
D000328:Adult; D001930:Brain Injuries / Q000503:physiopathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D002038:Bungarotoxins / Q000494:pharmacology; D002540:Cerebral Cortex / Q000098:blood supply / Q000737:chemistry* / Q000293:injuries*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000737:chemistry / Q000293:injuries; D006408:Hematoma, Subdural / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D015151:Immunoblotting; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010296:Parietal Lobe / Q000098:blood supply / Q000737:chemistry / Q000293:injuries; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000032:analysis; D009435:Synaptic Transmission / Q000502:physiology; D016708:Synaptophysin / Q000032:analysis; D013702:Temporal Lobe / Q000098:blood supply / Q000737:chemistry / Q000293:injuries; D014316:Tritium
D002038:Bungarotoxins; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D016708:Synaptophysin; D014316:Tritium; D009538:Nicotine; D002795:Choline O-Acetyltransferase