Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status.
Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.
Heyes
M P
MP
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Brew
B J
BJ
Martin
A
A
Price
R W
RW
Salazar
A M
AM
Sidtis
J J
JJ
Yergey
J A
JA
Mouradian
M M
MM
Sadler
A E
AE
Keilp
J
J
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003292:Convulsants / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D009498:Neurotoxins / Q000378:metabolism; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D012044:Regression Analysis; D015215:Zidovudine / Q000627:therapeutic use
D003292:Convulsants; D009498:Neurotoxins; D011805:Quinolinic Acids; D015215:Zidovudine; D017378:Quinolinic Acid