Mitochondrial DNA deletions in acute brain injury.
We hypothesized that generation of free radicals following acute brain injury leads to increased accumulation of mitochondrial DNA deletions. We determined the prevalence of two deletions (mtDNAdelta4977bp and mtDNAdelta7436hP) in brain from 53 patients with a short survival interval (mean 5 days) following transient global cerebral ischaemia due to cardiorespiratory arrest, 14 patients with long survival (mean 8.75 years) following traumatic brain injury and 43 age-matched controls. A higher prevalence of mtDNA delta4977bp was found in aged controls. There was a strong correlation between the presence of the two mtDNA deletions in individual cases (p < 0.05). The deletion prevalence did not differ significantly between short-term survivors of global ischaemia (57% mtDNAdelta4977bP, 62% mtDNAdelta7436bp) and controls (54% mtDNAdelta4977bp, 56% mtDNAdelta7436bp). Unexpectedly, there was a lower prevalence of deleted mtDNA in long-term survivors of traumatic brain injury (14.3% mtDNAdelta7436bp, p < 0.05) raising the possibility that free radical-induced accumulation of mtDNA damage may selectively influence the survival of mitochondria or their host.
McDonald
R P
RP
Department of Neuropathology, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital NHS Trust, UK.
Horsburgh
K J
KJ
Graham
D I
DI
Nicoll
J A
JA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005609:Free Radicals / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D004272:DNA, Mitochondrial; D005609:Free Radicals; D015345:Oligonucleotide Probes; D012333:RNA, Messenger