Reactive cell proliferation and microglia following injury to the rat brain

Abstract

The non-astrocytic cells which proliferate in the rat brain after the induction of an area of necrosis have been characterized and counted by means of combined in vivo bromodeoxyuridine (BrdU) administration and immunohistochemical demonstration of glial fibrillary acid protein (GFAP), vimentin, Ricinus communis agglutinin 120 (RCA-1), Griffonia simplicifolia B4 isolectin (GSI-B4), keratan sulphate (KS), carbonic anhydrase C (CA.C), transferrin (TF) and ferritin. Two days after the injury, 7.5% of the proliferating cells were GFAP-positive reactive astrocytes, 5.7% were RCA-1-positive cells and 17.4% were GSI-B4-positive cells. Lectin-binding cells had the microscopic and ultrastructural aspects of microglia; they proliferated around the needle track and in the corpus callosum. Microglia represented a large fraction of the proliferating cells. Evidence is presented for the origin of at least a proportion of perilesional astrocytes and microglia from the periventricular matrix, and of microglia from blood precursors. Other non-proliferating microglia cells transiently appeared in the normal brain around the wound, in agreement with the existence of two different microglia cell populations reacting with different modalities to an area of necrosis.

Metabolic and behavioral deficits following a routine surgical procedure in rats

“…At a cellular level, it has been shown that activated, proliferating microglia appear around the implant site as early as 1-day post implantation [18,21,42]. These activated microglia are thought to gradually diminish both excess fluid and cellular debris 6 -8 days after the implant, although necrotic tissue has been observed up to 42 days later [41,44].…”

Microglia/Macrophages Proliferate in Striatum and Neocortex but Not in Hippocampus after Brief Global Ischemia That Produces Ischemic Tolerance in Gerbil Brain

“…Markers for astrocytes (Chen et al, 1993;Petito et al, 1990), microglia (Giordana et al, 1994;Soriano et al, 1994), and oligodendrocytes (Hattori et al, 1992;Irving et al, 1997;Yam et al, 1997) provide useful indices of the glial responses to ischemia and other types of injury. One characteristic response that has been intensively studied is the activation of glia to form reactive microglia and reactive astrocytes after global and focal ischemia and many other types of brain injury.…”

Electron microscopic evidence for microglial phagocytic activity and cholinergic cell death after administration of the immunotoxin 192IgG-saporin in rat

“…Our electron microscopic data also did not reveal obvious signs of cell shrinkage and nuclear chromatin condensation, suggesting that 192IgG-saporin exerts its cell-damaging action preferentially by induction of necrosis characterized by swelling and cell rupture. Like most other experimental models (Kaur and Ling, 1990;Gehrmann et al, 1992;Giordana et al, 1994;Gehrmann and Kreutzberg, 1995;for review, see Streit and Kreutzberg, 1988;Kreutzberg, 1996) we could also demonstrate a graded response of microglia to the immunotoxin-induced injury. The marker which has been used throughout the present investigation to identify microglia was an HRP-conjugated lectin (the isolectin B 4 derived from Griffonia simplicifolia), which specifically binds a-D-galactose containing glycoconjugates in their plasma membrane and has been shown to stain selectively rat microglial cells in normal as well as in pathologically altered brains (Streit and Kreutzberg, 1987;Ashwell, 1989;Streit, 1990Streit, , 1995.…”

“…The number of microglial cells was strikingly increased at day 7 postlesion. Many other studies documented a graded microglial response to experimental brain injury over the first weeks following mechanical lesions (Graeber et al, 1988;Giordana et al, 1994; for review, see Streit and Kreutzberg, 1987;Leong and Ling, 1992;Kreutzberg, 1996) and excitotoxic lesions (Kaur and Ling, 1990;Marty et al, 1991;Kaur et al, 1992).…”