Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome

Immunohistochemical localization of serum proteins in postmortem brain

Carol Petito, Kevin S. Cash

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

Abnormalities in the blood-brain barrier (BBB) may be important in mediating some of the tissue damage that accompanies human immunodeficiency virus (HIV) infection of the brain, as well as in facilitating viral entry into the central nervous system. Accordingly, immunohistochemical detection of fibrinogen (FIB) and immunoglobulin G (IgG) was used as a marker of vascular permeability in formalin-fixed, paraffin-embedded brains of patients with acquired immunodeficiency syndrome (AIDS) who had HIV encephalitis (HIVE) (n = 17) and those who did not have HIVE (n = 16); nonimmunosuppressed patients served as control subjects (n = 22). The sex ratios and postmortem intervals were similar in all groups (p > 0.05), but the age of the two AIDS groups were younger than the control group (43.2 and 40.9 versus 62.5 yr; p < 0.05). The two AIDS groups had higher immunostaining for FIB and IgG than the control group (p < 0.001 and p < 0.0001, respectively) but did not differ from one another. Furthermore, the two AIDS groups had a significantly higher incidence of combined extravasation of both FIB and IgG, whereas the control group had a significantly higher incidence of negative staining for both proteins (p < 0.002). More than 95% of the microglial nodules of HIV were negative for serum proteins; however, all focal lesions with tissue necrosis, including lymphoma, opportunistic infections, and HIV (rarely), contained extravasated serum proteins. These results indicate that a diffuse BBB leak is present in approximately 50% of all patients with AIDS at the time of autopsy and may be seen in the absence of any other brain pathology, including HIVE. In contrast, focal lesions, including those of HIVE, are associated with BBB changes only when necrosis is present. The pathogenesis of the diffuse leak is unknown but may be related to circulating cytokines. Diffuse BBB breakdown may contribute not only to facilitated viral entry into brain, but also to the diffuse myelin pallor and gliosis common to all patients with AIDS.

Original languageEnglish
Pages (from-to)658-666
Number of pages9
JournalAnnals of Neurology
Volume32
Issue number5
StatePublished - Nov 1 1992
Externally publishedYes

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Blood-Brain Barrier
Blood Proteins
Acquired Immunodeficiency Syndrome
HIV
Encephalitis
Brain
Fibrinogen
Immunoglobulin G
Control Groups
Necrosis
Pallor
Negative Staining
Gliosis
Incidence
Opportunistic Infections
Sex Ratio
Capillary Permeability
Virus Diseases
Myelin Sheath
Paraffin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome : Immunohistochemical localization of serum proteins in postmortem brain. / Petito, Carol; Cash, Kevin S.

In: Annals of Neurology, Vol. 32, No. 5, 01.11.1992, p. 658-666.

Research output: Contribution to journalArticle

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