Blood-brain barrier disruption in simian immunodeficiency virus encephalitis.
Infected monocyte-derived macrophages (MDM) are thought by some investigators to play a central role in the neuropathogenesis of human immunodeficiency virus encephalitis (HIVE). It was recently proposed that these cells gain access to the central nervous system (CNS) through disruptions in blood-brain barrier (BBB) tight junctions, which occur in HIVE in association with accumulation of activated, HIV-1-infected, perivascular macrophages and serum protein extravasation (Am J Pathol 1999, 155: 1915-27). The present study tested this hypothesis in basal ganglia tissue from simian immunodeficiency virus (SIV)-infected macaques with encephalitis by examining vessels for immunohistochemical alterations in the tight junction-associated proteins, occludin and zonula occludens-1 (ZO-1). Compared to non-infected macaques and SIV-infected macaques without encephalitis, cerebral vessels from macaques with SIVE showed fragmentation and decreased immunoreactivity for both tight junction proteins. These alterations were associated with accumulation of perivascular macrophages and aberrant occludin and ZO-1 immunoreactivity within these cells. In addition, perivascular extravasation of fibrinogen, a plasma protein, and a change from a strong linear staining pattern to a more irregular pattern of glucose transporter isoform-1 (GLUT-1), a metabolic BBB marker, were observed in regions with vascular tight junction protein alterations. These findings demonstrate that tight junction disruption occurs in SIVE in association with perivascular macrophage accumulation. While it cannot be ascertained from these studies whether such changes precede macrophage infiltration, or are secondary to the chronic presence of macrophages around cerebral vessels, disruptions in BBB integrity could serve as portals for additional accumulation of perivascular macrophages in SIVE.
Luabeya
M K
MK
Department of Pathology (Division of Neuropathology), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Dallasta
L M
LM
Achim
C L
CL
Pauza
C D
CD
Hamilton
R L
RL
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier; D004660:Encephalitis / Q000821:virology*; D051272:Glucose Transporter Type 1; D017958:Lentiviruses, Primate; D008253:Macaca mulatta; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012016:Reference Values; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins