Morphology of reactive microglia in the injured cerebral cortex. Fractal analysis and complementary quantitative methods

Sołtys, Zbigniew; Ziaja, Marek; Pawliński, Rafał; Setkowicz, Zuzanna; Janeczko, Krzysztof

doi:10.1002/1097-4547(20010101)63:1<90::aid-jnr11>3.0.co;2-9

Cited by 171 publications

(160 citation statements)

References 35 publications

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“…189 Numbers of microglia along the cell death (M1) and repair promoting (M2) phenotypic spectrum depend on TBI severity and kinetics of regulation. 188,190 The "immunoexcitotoxicity" theory suggests an alternative to the traditional and functionally distinct M1-M2 phenotypic polarization. Microglia are said to move from their resting and ramified state to one, where they swell with proinflammatory cytokines, remaining "primed" for action in the absence of inflammatory resolution.…”

Section: Microglial Activationmentioning

confidence: 96%

Repeated mild traumatic brain injury: potential mechanisms of damage

2016

Cell Transplant

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Mild traumatic brain injury (mTBI) represents a significant public healthcare concern, accounting for the majority of all head injuries. While symptoms are generally transient, some patients go on to experience long-term cognitive impairments and additional mild impacts can result in exacerbated and persisting negative outcomes. To date, studies using a range of experimental models have reported chronic behavioral deficits in the presence of axonal injury and inflammation following repeated mTBI; assessments of oxidative stress and myelin pathology have thus far been limited. However, some models employed induced acute focal damage more suggestive of moderate-severe brain injury and are therefore not relevant to repeated mTBI. Given that the nature of mechanical loading in TBI is implicated in downstream pathophysiological changes, the mechanisms of damage and chronic consequences of single and repeated closed-head mTBI remain to be fully elucidated. This review covers literature on potential mechanisms of damage following repeated mTBI, integrating known mechanisms of pathology underlying moderate-severe TBIs, with recent studies on adult rodent models relevant to direct impact injuries rather than blast-induced damage. Pathology associated with excitotoxicity and cerebral blood flow-metabolism uncoupling, oxidative stress, cell death, blood-brain barrier dysfunction, astrocyte reactivity, microglial activation, diffuse axonal injury, and dysmyelination is discussed, followed by a summary of functional deficits and preclinical assessments of therapeutic strategies. Comprehensive characterization of the pathology underlying delayed and persisting deficits following repeated mTBI is likely to facilitate further development of therapeutic strategies to limit long-term sequelae.

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Section: Microglial Activationmentioning

confidence: 96%

Repeated mild traumatic brain injury: potential mechanisms of damage

2016

Cell Transplant

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“…18 Microglial phenotypic classification was based on the length and thickness of the projections, the number of branches and the size of the cell body, as previously described. 51,52 The estimated number of microglia in each phenotypic class was divided by the volume of the region of interest to obtain the cellular density expressed in cells/mm 3 . Neurolucida software (MBF Biosciences) was used to create reconstructions of microglia at different stages of activation after injury by tracing the cell bodies and dendrites.…”

Section: Immunohistochemistry Image Acquisition and Quantificationmentioning

confidence: 99%

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

Zhao

Kumar

et al. 2016

Journal of Neurotrauma

105

100

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Clinical and experimental studies show that spinal cord injury (SCI) can cause cognitive impairment and depression that can significantly impact outcomes. Thus, identifying mechanisms responsible for these less well-examined, important SCI consequences may provide targets for more effective therapeutic intervention. To determine whether cognitive and depressive-like changes correlate with injury severity, we exposed mice to sham, mild, moderate, or severe SCI using the Infinite Horizon Spinal Cord Impactor and evaluated performance on a variety of neurobehavioral tests that are less dependent on locomotion. Cognitive impairment in Y-maze, novel objective recognition, and step-down fear conditioning tasks were increased in moderate-and severe-injury mice that also displayed depressive-like behavior as quantified in the sucrose preference, tail suspension, and forced swim tests. Bromo-deoxyuridine incorporation with immunohistochemistry revealed that SCI led to a long-term reduction in the number of newly-generated immature neurons in the hippocampal dentate gyrus, accompanied by evidence of greater neuronal endoplasmic reticulum (ER) stress. Stereological analysis demonstrated that moderate/severe SCI reduced neuronal survival and increased the number of activated microglia chronically in the cerebral cortex and hippocampus. The potent microglial activator cysteine-cysteine chemokine ligand 21 (CCL21) was elevated in the brain sites after SCI in association with increased microglial activation. These findings indicate that SCI causes chronic neuroinflammation that contributes to neuronal loss, impaired hippocampal neurogenesis and increased neuronal ER stress in important brain regions associated with cognitive decline and physiological depression. Accumulation of CCL21 in brain may subserve a pathophysiological role in cognitive changes and depression after SCI.

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“…Microglial phenotypic classification was based on the length and thickness of the projections, the number of branches and the size of the cell body as previously described. 13,14,20 Hippocampal subregions were counted as a whole and the volume of the region of interest was measured using the Cavalieri estimator method with a grid spacing of 100 mm for the hippocampus. The estimated number of microglia in each phenotypic class was divided by the volume of the hippocampus to obtain the cellular density expressed in counts/mm 3 .…”

Section: Immunohistochemistrymentioning

confidence: 99%

Repeated Mild Traumatic Brain Injury Causes Chronic Neuroinflammation, Changes in Hippocampal Synaptic Plasticity, and Associated Cognitive Deficits

Aungst

Kabadi

Thompson

et al. 2014

J Cereb Blood Flow Metab

209

157

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Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration.

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Morphology of reactive microglia in the injured cerebral cortex. Fractal analysis and complementary quantitative methods

Cited by 171 publications

References 35 publications

Repeated mild traumatic brain injury: potential mechanisms of damage

Repeated mild traumatic brain injury: potential mechanisms of damage

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

Repeated Mild Traumatic Brain Injury Causes Chronic Neuroinflammation, Changes in Hippocampal Synaptic Plasticity, and Associated Cognitive Deficits

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