Rapid and Widespread Microglial Activation Induced by Traumatic Brain Injury in Rat Brain Slices

Abstract

In order to assess the role of circulating blood in early microglial activation after traumatic brain injury (TBI), controlled cortical impact injury was applied to adult rat brain slices (400 microm in thickness) and the microglial response was examined. The complement receptor (CR3) expression and morphological transformation of the microglia were evaluated by OX42 immunohistochemistry. At 5 min following injury, activated microglia with intense CR3 expression appeared throughout the hemisphere on the injured side. In contrast, the morphology and CR3 expression of the microglia on the contralateral side were indistinguishable from those of the resident ramified microglia seen in normal brains. At 30 min following injury, microglial activation was more pronounced on the injured side, while the microglia on the contralateral side still retained a ramified morphology. These results are consistent with our previous observations made in in vivo experiments, which indicate that, as the brain slice paradigm excludes variables arising from the circulating blood, the rapid and widespread microglial activation observed following TBI can not be attributed exclusively to the infiltration of blood-borne macrophages or molecules. Rather this activation is most likely caused by intrinsic mechanisms within the brain tissue, such as traumatic depolarization.

Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices

“…Several previous studies have shown that brain resident phagocytes (microglia) become activated in CNS tissue slice preparations, presumably in response to neuronal injury and death (Smith et al, 1990;Brockhaus et al, 1996;Hailer et al, 1996;Czapiga and Colton, 1999;Koshinaga et al, 2000;Stence et al, 2001). Although by 1 DIV, most microglia had a morphological appearance of being fully activated, our time-lapse observations showed that individual microglia differed dramatically in their motile behaviors.…”

Regulating Factors for Microglial Activation.

“…6) In addition to the above progressive neurodegeneration in the CNS, microglial activation is proposed to be involved in the secondary damage following the primary damage after traumatic brain injury. 7) Microglial activation is also believed to play an important role in pathological pain mechanisms such as nociceptive abnormality and hyperalgesia. 8) Even in psychiatric illnesses, it is reported that mononuclear phagocytes accumulate in the cerebrospinal fluid of schizophrenic patients during acute psychotic episodes, 9) and microglial activation is often observed in the postmortem pathohistologic examination of patients with schizophrenia.…”

Uncovering the Path to Neurodegeneration from Playingfield to Battlefield

“…In brain donors and experimental animal models, TBI has been associated with increased reactivity of microglia [81,82]. Microglia are the resident macrophages of the brain.…”