Evaluation of early chronic functional outcomes and their relationship to pre-frontal cortex and hippocampal pathology following moderate-severe traumatic brain injury

Arulsamy, Alina; Teng, Jason; Colton, Holly; Corrigan, Frances; Collins-Praino, Lyndsey E.

doi:10.1016/j.bbr.2018.04.009

Cited by 23 publications

(21 citation statements)

References 66 publications

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“…Although this study did not directly assess behaviour, we have previously reported that at one-month post-injury, animals showed no cognitive deficits on the Y Maze, anxiety deficits on the Elevated Plus Maze, or locomotor deficits on the rotarod, but did have increased depressive-like behaviour on the forced swim test (Arulsamy et al., 2018). Indeed, even at 12 months post-injury, only subtle executive function deficits were noted post-TBI, although the methods used were inadequate to determine whether depressive-like behaviour was present (Arulsamy et al., 2019).…”

Section: Discussionmentioning

confidence: 96%

“…These DTI changes may also be the result of underlying neuroinflammation, as this pathology within the grey matter was supported via the examination of the number of activated microglia, as seen as a change in morphology, which found increases within the cortex, hypothalamus, hippocampus, midbrain, and thalamus, primarily peaking at 24 h post-injury. This phenomenon has been investigated in different animal models of TBI showing persistent and prolonged microglia activation weeks (Arulsamy et al., 2018; Donat et al., 2017; Elliott et al., 2011), months (Arulsamy et al., 2018; Glushakova et al., 2014; Holmin and Mathiesen, 1999), and even years (Loane et al., 2014) following TBI. TBI leads to the initiation of an inflammatory in response to cellular damage and an associated release of factors that act as damage-associated molecules (Corrigan et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

“…All animals were resuscitated using compressed air (0.8 L/min nitrogen; 0.2 L/min oxygen) to avoid aponia which could lead to high mortality rates (Plummer et al., 2018). Successful induction of moderate to severe TBI was assessed 24 h later by rotarod scores<100, weight reduction of 5–10% and clinical signs (paresis and hunched posture) (Arulsamy et al., 2018).…”

Section: Methodsmentioning

confidence: 99%

“…Sections were counterstained with hematoxylin. Slides were digitally scanned using a Nanozoomer, viewed with the associated NDP view software, with images exported for analysis with ImageJ (Arulsamy et al., 2018).…”

Section: Methodsmentioning

confidence: 99%

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Evaluating spatiotemporal microstructural alterations following diffuse traumatic brain injury

Mohamed

Corrigan

Collins-Praino

et al. 2020

NeuroImage: Clinical

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BackgroundDiffuse traumatic brain injury (TBI) is known to lead to microstructural changes within both white and grey matter detected in vivo with diffusion tensor imaging (DTI). Numerous studies have shown alterations in fractional anisotropy (FA) and mean diffusivity (MD) within prominent white matter tracts, but few have linked these to changes within the grey matter with confirmation via histological assessment. This is especially important as alterations in the grey matter may be predictive of long-term functional deficits.MethodsA total of 33 male Sprague Dawley rats underwent severe closed-head TBI. Eight animals underwent tensor-based morphometry (TBM) and DTI at baseline (pre-TBI), 24 hours (24 h), 7, 14, and 30 days post-TBI. Immunohistochemical analysis for the detection of ionised calcium-binding adaptor molecule 1 (IBA1) to assess microglia number and percentage of activated cells, β-amyloid precursor protein (APP) as a marker of axonal injury, and myelin basic protein (MBP) to investigate myelination was performed at each time-point.ResultsDTI showed significant alterations in FA and RD in numerous white matter tracts including the corpus callosum, internal and external capsule, and optic tract and in the grey-matter in the cortex, thalamus, and hippocampus, with the most significant effects observed at 14 D post-TBI. TBM confirmed volumetric changes within the hippocampus and thalamus. Changes in DTI were in line with significant axonal injury noted at 24 h post-injury via immunohistochemical analysis of APP, with widespread microglial activation seen within prominent white matter tracts and the grey matter, which persisted to 30 D within the hippocampus and thalamus. Microstructural alterations in MBP+ve fibres were also noted within the hippocampus and thalamus, as well as the cortex.ConclusionThis study confirms the widespread effects of diffuse TBI on white matter tracts which could be detected via DTI and extends these findings to key grey matter regions, with a comprehensive investigation of the whole brain. In particular, the hippocampus and thalamus appear to be vulnerable to ongoing pathology post-TBI, with DTI able to detect these alterations supporting the clinical utility in evaluating these regions post-TBI.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Evaluating spatiotemporal microstructural alterations following diffuse traumatic brain injury

Mohamed

Corrigan

Collins-Praino

et al. 2020

NeuroImage: Clinical

Self Cite

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“…Neurological disorders typically present activation of glial cells, including their release of pro-inflammatory cytokines and chemokines. This is the normal CNS response to protect neural tissue and is mainly regulated by microglia and astroglia [ 27 , 28 , 29 , 30 , 31 , 32 , 60 , 61 ] ( Figure 2 ). However, while acute glial activation is protective by design, failure of this protective acute activity may consequently lead to chronic glial activation, i.e., to enduring inflammation of neural tissue, and even cell death.…”

Section: Brain Cell Types and The Effects Of Raloxifenementioning

confidence: 99%

Raloxifene as Treatment for Various Types of Brain Injuries and Neurodegenerative Diseases: A Good Start

Veenman

2020

IJMS

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Recent studies have shown that the selective estrogen receptor modulator (SERM) raloxifene had pronounced protective effects against progressing brain damage after traumatic brain injury (TBI) in mice. These studies, indicating beneficial effects of raloxifene for brain health, prompted the study of the history and present state of knowledge of this topic. It appears that, apart from raloxifene, to date, four nonrelated compounds have shown comparable beneficial effects—fucoidan, pifithrin, SMM-189 (5-dihydroxy-phenyl]-phenyl-methanone), and translocator protein (TSPO) ligands. Raloxifene, however, is ahead of the field, as for more than two decades it has been used in medical practice for various chronic ailments in humans. Thus, apart from different types of animal and cell culture studies, it has also been assessed in various human clinical trials, including assaying its effects on mild cognitive impairments. Regarding cell types, raloxifene protects neurons from cell death, prevents glial activation, ameliorates myelin damage, and maintains health of endothelial cells. At whole central nervous system (CNS) levels, raloxifene ameliorated mild cognitive impairments, as seen in clinical trials, and showed beneficial effects in animal models of Parkinson’s disease. Moreover, with stroke and TBI in animal models, raloxifene showed curative effects. Furthermore, raloxifene showed healing effects regarding multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) in cell culture. The adverse biological signals typical of these conditions relate to neuronal activity, neurotransmitters and their receptors, plasticity, inflammation, oxidative stress, nitric oxide, calcium homeostasis, cell death, behavioral impairments, etc. Raloxifene favorably modulates these signals toward cell health—on the one hand, by modulating gene expression of the relevant proteins, for example by way of its binding to the cell nuclear estrogen receptors ERα and ERβ (genomic effects) and, on the other hand (nongenomic effects) by modulation of mitochondrial activity, reduction of oxidative stress and programmed cell death, maintaining metabolic balance, degradation of Abeta, and modulation of intracellular cholesterol levels. More specifically regarding Alzheimer’s disease, raloxifene may not cure diagnosed Alzheimer’s disease. However, the onset of Alzheimer’s disease may be delayed or arrested by raloxifene’s capability to attenuate mild cognitive impairment. Mild cognitive impairment is a condition that may precede diagnosis of Alzheimer’s disease. In this review, relatively new insights are addressed regarding the notion that Alzheimer’s disease can be caused by bacterial (as well as viral) infections, together with the most recent findings that raloxifene can counteract infections of at least some bacterial and viral strains. Thus, here, an overview of potential treatments of neurodegenerative disease by raloxifene is presented, and attention is paid to subcellular molecular biological pathways that may be involved.

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Long-Term Sequelae of Traumatic Brain Injury in Rats: A Morphological, Behavioral, and Electrophysiological Study

Komoltsev

Volkova

Levshina

et al. 2021

Neurosci Behav Physi

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Evaluation of early chronic functional outcomes and their relationship to pre-frontal cortex and hippocampal pathology following moderate-severe traumatic brain injury

Cited by 23 publications

References 66 publications

Evaluating spatiotemporal microstructural alterations following diffuse traumatic brain injury

Evaluating spatiotemporal microstructural alterations following diffuse traumatic brain injury

Raloxifene as Treatment for Various Types of Brain Injuries and Neurodegenerative Diseases: A Good Start

Long-Term Sequelae of Traumatic Brain Injury in Rats: A Morphological, Behavioral, and Electrophysiological Study

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