Korean J Anat.  2004 Aug;37(4):329-336.

Neuroglial Proliferative Activity Following Medial Forebrain Bundle Axotomy

Affiliations
  • 1Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Korea. bpcho@wonju.yonsei.ac.kr
  • 2Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Wonju, Korea.

Abstract

Changes in morphology, immunophenotypes and proliferative activity of neuroglia are key features in most forms of CNS pathology. We compared proliferative activity of neuroglial cells in response to two different types of brain injury induced by medial forebrain bundle (MFB) axotomy. In the cannula track where acute necrosis occurs due to mechanical lesion caused by cannula inserted to incise the MFB, many BrdU-immunoreactive (ir) cells appeared around the cannula track already at 1 day post-lesion (1 dpl). Their number significantly increased by 7 dpl and then decreased, but considerable number of BrdU-ir cells was still found at 14 dpl. Some of the BrdU-ir cells were double-labeled with either OX-42 or GFAP. This finding suggests that both microglia and astrocytes are activated and proliferate immediately after the mechanical damage, and the proliferative activity is maintained in a considerable number of these cells by 14 dpl. In general, the main cell type showing BrdU immunoreactivity was amoeboid microglia within the necrotic zone immediately surrounding the cannula track, and was astrocytes in the periphery of the necrotic zone more or less apart from the cannula track. Previously, we reported that MFB axotomy induces apoptosis of dopaminergic (DA) neurons in the substantia nigra (SN). In the SN where axotomized DA neurons undergo apoptosis, only a few BrdU-ir cells were found at 1 dpl. Their number increased gradually from 3 dpl and peaked at 7 dpl, then significantly reduced at 14 dpl. Most of them were double-labeled with OX -42-positive ramified microglia but not with GFAP. This data indicates that microglia but not astrocyte are the cell type that proliferate in response to apoptotic neuronal cell death, and their morphology and proliferative activity are different from those observed in the cannula track. Meanwhile, in the both cannula track and SN, some BrdU-ir cells were thought to be neither GFAP-positive nor OX-42-positive, and thus they were presumed to be infiltrated peripheral immune cells. These results demonstrate that different types of neuronal cell death are accompanied with different neurogilal proliferative activities.

Keyword

Microglia; Astrocyte; MFB; Axotomy; Substantia nigra; BrdU

MeSH Terms

Apoptosis
Astrocytes
Axotomy*
Brain Injuries
Bromodeoxyuridine
Catheters
Cell Death
Medial Forebrain Bundle*
Microglia
Necrosis
Neuroglia
Neurons
Pathology
Substantia Nigra
Bromodeoxyuridine
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