PK ('peripheral benzodiazepine')--binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia.
The isoquinoline PK11195 has been suggested as a marker of glial pathology in the lesioned brain. The aim of the present study is to clarify the precise cellular location of its binding site in the central nervous system. Here, we report that in the facial nucleus after facial nerve axotomy-a lesion causing a retrograde neuronal reaction without nerve cell death while keeping the blood-brain barrier intact--activated microglia are the predominant source of lesion-induced increases of PK11195 binding. Likewise, increased PK11195 binding is seen in the gracile nucleus after anterograde neuronal injury following sciatic nerve transection. The peak of PK11195 binding, using the single isomer R-PK11195, was observed 4 days after the peripheral nerve lesion, consistent with the well-known time course of microglial activation. Photoemulsion microautoradiography confirmed the restriction of PK11195 binding to activated microglia. The increase of PK11195 binding in the facial nucleus seen after selective cell death of facial motoneurons by retrograde suicide transport of toxic ricin, a lesion that is accompanied by the rapid transformation of microglia into phagocytes, was no higher than that seen following axotomy. This suggests that the full transformation of microglia into parenchymal phagocytes is not necessary to reach maximal levels of PK11195 binding. PK11195, therefore, is a well-suited marker to detect microglial activation in areas of subtle brain pathology, where neither a disturbance of the blood-brain barrier function nor the presence of macrophages and inflammatory cells indicate an on-going disease process.
Banati
R B
RB
MRC Cyclotron Unit, CSC, RPMS, Hammersmith Hospital, London, UK.
Myers
R
R
Kreutzberg
G W
GW
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D005154:Facial Nerve / Q000502:physiology; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D010586:Phagocytes; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology; D013997:Time Factors; D014316:Tritium
D007546:Isoquinolines; D011963:Receptors, GABA-A; D014316:Tritium; C037850:PK 11195