The Microglial Reaction in the Rat Dorsal Hippocampus following Transient Forebrain Ischemia

Abstract

We have examined the distribution and time course of the microglial reaction in the rat dorsal hippocampus after 25-min transient forebrain ischemia (four-vessel occlusion model). Microglial cells were visualized in brain sections using lectin staining with the Griffonia simplicifolia B4-isolectin following intervals of reperfusion ranging from 20 min to 4 weeks. Increased staining of microglial cells was detected in the dentate hilus and area CA1 as early as 20 min after reperfusion. These same regions demonstrated more intense microglial staining after 24 h. The strongest microglial reaction was observed 4-6 days after reperfusion when reactive microglia were abundant throughout all laminae of CA1 and the dentate hilus. Following longer reperfusion intervals, the microglial reaction became less intense; however, it remained above normal levels until the end of the fourth week. At all time points examined, microglial reactivity in the CA3 pyramidal and dentate granule cell layers was considerably lower than that observed in CA1 and dentate hilus. Our results are consistent with the known serial pathological changes associated with cerebral ischemia, but, in addition, show that the examination of the microglial reaction provides an extremely sensitive indicator of subtle and morphologically nonapparent neuronal damage during the early stages of injury.

Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

“…There is increasing evidence that microglial cells contribute to delayed neuronal death. Recruitment and activation of microglial cells gradually increase within the hippocampal CA1 area over 24 h after transient forebrain ischemia, before the degeneration of neurons [28]. Endangered neurons can release proinflammatory chemokines such as monocyte chemoattractant protein-1 (MCP-1/CCL2) and secondary lymphoid-tissue chemokine (SLC/CCL21).…”

Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury

“…Microglia, immune cells in the CNS, have been reported to proliferate after CNS damage. 4 These proliferated microglia possibly accelerate neuronal damage by releasing toxic substances. [6][7][8] We previously reported that microglial proliferation and activation were observed in the damaged spinal cord, and that the time course of the progress of hind-limb function loss was quite similar to that of the microglia proliferation in spinal cord after a compression injury.…”

“…Under conditions such as ischemia 4 and trauma, 5 microglia proliferate and are activated. These pathologically activated microglia accelerate neuronal damage by releasing nitric oxide, superoxide and inflammatory cytokines such as TNF-a.…”

Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia

“…Post-ischemic inflammation has been suggested to contribute to delayed neuronal damage at the periphery of infarcts (Stoll et al, 1998), implicating microglia as important mediators in ischemic brain damage. Microglia become activated in response to varying severities of ischemia leading to upregulation of major histocompatibility complex (MHC) class I antigen (Morioka et al, 1991) and nitric oxide synthase (NOS; Yamashita et al, 1995). In the latter case, it is suggested that increased NO production by activated microglia may contribute to neuronal death, thus providing a putative link between microglial activation and post-ischemic neuronal damage.…”