The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice

Ahmed, Farid; Plantman, Stefan; Černak, Ibolja; Agoston, Denes V.

doi:10.3389/fneur.2015.00114

Cited by 59 publications

(62 citation statements)

References 109 publications

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“…HIF-1 α is a transcription factor that is involved in several injury modalities where hypoxia occurs, including TBI [51]. Even though HIF-1 α has been shown to play a role in TBI progression and cerebral ischemia, few studies have examined its role after mTBI and it has not been investigated in relation to BPT [52, 53]. Delayed opening of the BBB, that is, only after HIF-1 α was already stabilized, suggested barrier stability is mediated via one or more HIF-1 α effectors [54].…”

Section: Discussionmentioning

confidence: 99%

Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

Hubbard

Greenberg

Norris

et al. 2017

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical models simulating BPT, which is crucial to identifying unique injury mechanisms of BPT and its management. To meet this need, our group characterized a rodent model of BPT and compared results to a blast-induced mTBI model. Open field (OF) performance trials were performed on rodents at 7 days after injury. Immunohistochemistry was performed to evaluate cellular outcome at day seven following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3 expression), and vascular damage (SMI-71) were significantly elevated in BPT compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1α and VEGF) were higher only after BPT. This study highlights the need for unique therapeutics and prehospital management when handling BPT.

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Section: Discussionmentioning

confidence: 99%

Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

Hubbard

Greenberg

Norris

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…40 Increase in both plasma level of S100b and cortex level of NSE increase have been used as specific markers of astroglial plasticity, particularly in BBB opening and brain injury. [41][42][43] In this study, the co-administered treatment significantly led to increase in both S100b abundance in the plasma of the PD rat brain compared to the untreated group and even the L-dopa single treatment. However, NSE level in the cortex in the models with the co-administration was significantly higher than the untreated ones but lower than the L-dopa-treated ones, which might imply the BBB opening with less brain injury.…”

Section: Discussionmentioning

confidence: 53%

β‐asarone and levodopa co‐administration increase striatal dopamine level in 6‐hydroxydopamine induced rats by modulating P‐glycoprotein and tight junction proteins at the blood‐brain barrier and promoting levodopa into the brain

Huang

Deng

et al. 2016

Clin Exp Pharma Physio

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Levodopa (L-dopa) is widely considered as one of the most effective drug constituents in the treatment of Parkinson's disease (PD), but the blood-brain barrier (BBB) permeability of L-dopa is <5%, which causes low efficacy. Neuroprotective effects of β-asarone on 6-hydroxydopamine (6-OHDA)-induced PD rats were demonstrated by our previous studies. Co-administration of β-asarone and L-dopa has not been explored until being investigated on PD rats in this study. PD rats were divided into four groups: untreated, L-dopa-treated, β-asarone-treated and co-administered-treated groups. All of the treatments were administered to the rats twice per day for 30 days. The L-dopa, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), S100β and neuron-specific enolase (NSE) levels were subsequently determined. The P-glycoprotein (P-gp), zonula occludens-1 (ZO-1), claudin-5, occludin and actin expression was also assessed in cortex. Changes in BBB ultrastructure were observed using transmission electron microscopy. Our results showed that the co-administered treatment increased levels of L-dopa, DA, DOPAC and HVA in striatum, and S100β in plasma, but down-regulated NSE, P-gp, ZO-1, occludin, actin and claudin-5 in cortex. Crevices were observed between capillary endothelial cells at intercellular tight junction of the striatum in co-administered-treated group, while the endothelial cells in untreated group were tightly jointing each other. In addition, the correlations of L-dopa or DA and P-gp or tight junction proteins respectively were significantly negative in co-administered- and β-asarone-treated groups. These findings suggest that co-administered treatment may enhance the L-dopa BBB permeability and attenuate brain injury, which may be beneficial to PD treatment.

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“…Following a single, low-intensity blast TBI in mice, serum tau is significantly elevated two hours and one day following injury (Ahmed et al , 2015). However, non-significant elevations in serum tau were sustained for at least one month following injury (Ahmed et al , 2015); a time course which parallels findings in mice receiving a mild blast-injury in which phosphorylated and cleaved forms of neuronal tau were increased 24h and one month post-injury (Huber et al , 2013). Therefore, increases in serum tau following blast TBI are likely to be representative of pathophysiological changes to tau in the brain tissue.…”

Section: Tau - a Biomarker For Tbimentioning

confidence: 99%

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

Kulbe

Hall

2017

Progress in Neurobiology

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In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, football, football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression.

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The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice

Cited by 59 publications

References 109 publications

Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

β‐asarone and levodopa co‐administration increase striatal dopamine level in 6‐hydroxydopamine induced rats by modulating P‐glycoprotein and tight junction proteins at the blood‐brain barrier and promoting levodopa into the brain

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

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