Hypothermia pretreatment improves cognitive impairment via enhancing synaptic plasticity in a traumatic brain injury model

Liu, Bingjin; Wang, Lin; Cao, Yun; Xu, Weiqi; Shi, Fang-Xiao; Tian, Qing; Zhou, Xin‐Wen

doi:10.1016/j.brainres.2017.07.008

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…TBI, in particular, has been reported to acutely induce extensive dendritic de-arborization and a reduction in synapse number (Winston et al, 2013; Wen et al, 2017). Such a decline in synaptic strength has been proposed to underpin, at least in part, TBI mediated impairments in LTP and cognition (Liu et al, 2017). Indeed, synaptic loss, rather than either neurodegeneration or the formation of amyloid pathology, has been demonstrated to best associate with cognitive impairment (Selkoe, 2002; D’Amelio et al, 2011; Marchetti and Marie, 2011).…”

Section: Discussionmentioning

confidence: 99%

(-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice

Lecca

Bader

Tweedie

et al. 2019

Neurobiology of Disease

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Mild traumatic brain injury (mTBI) is a risk factor for neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). TBI-derived neuropathologies are promoted by inflammatory processes: chronic microgliosis and release of pro-inflammatory cytokines that further promote neuronal dysfunction and loss. Herein, we evaluated the effect on pre-programmed cell death/neuroinflammation/synaptic integrity and function of (−)-Phenserine tartrate (Phen), an agent originally developed for AD. This was studied at two clinically translatable doses (2.5 and 5.0 mg/kg, BID), in a weight drop (concussive) mTBI model in wild type (WT) and AD APP/PSEN1 transgenic mice. Phen mitigated mTBI-induced cognitive impairment, assessed by Novel Object Recognition and Y-maze behavioral paradigms, in WT mice. Phen fully abated mTBI-induced neurodegeneration, evaluated by counting Fluoro-Jade C-positive (FJC+) cells, in hippocampus and cortex of WT mice. In APP/PSEN1 mice, degenerating cell counts were consistently greater across all experimental groups vs. WT mice. mTBI elevated FJC+ cell counts vs. the APP/PSEN1 control (sham) group, and Phen similarly mitigated this. Anti-inflammatory effects on microglial activation (IBA1-immunoreactivity (IR)) and the pro-inflammatory cytokine TNF-α were evaluated. mTBI increased IBA1-IR and TNF-α/IBA1 colocalization vs. sham, both in WT and APP/PSEN1 mice. Phen decreased IBA1-IR throughout hippocampi and cortices of WT mice, and in cortices of AD mice. Phen, likewise, reduced levels of IBA1/TNF-α-IR colocalization volume across all areas in WT animals, with a similar trend in APP/PSEN1 mice. Actions on astrocyte activation by mTBI were followed by evaluating GFAP, and were similarly mitigated by Phen. Synaptic density was evaluated by quantifying PSD-95+ dendritic spines and Synaptophysin (Syn)-IR. Both were significantly reduced in mTBI vs. sham in both WT and APP/PSEN1 mice. Phen fully reversed the PSD-95+ spine loss in WT and Syn-IR decrease in both WT and APP/PSEN1 mice. To associate immunohistochemical changes in synaptic markers with function, hippocampal long term potentiation (LTP) was induced in WT mice. LTP was impaired by mTBI, and this impairment was mitigated by Phen. In synopsis, clinically translatable doses of Phen ameliorated mTBI-mediated pre-programmed cell death/neuroinflammation/synaptic dysfunction in WT mice, consistent with fully mitigating mTBI-induced cognitive impairments. Phen additionally demonstrated positive actions in the more pathologic brain microenvironment of AD mice, further supporting consideration of its repurposing as a treatment for mTBI.

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Section: Discussionmentioning

confidence: 99%

(-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice

Lecca

Bader

Tweedie

et al. 2019

Neurobiology of Disease

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“…Mice in the HT groups were cooled twice (once a week) two weeks before TBI treatment. TBI and sham‐injury procedures operated in accordance with previously described methods 7,35 . In short, mice were anaesthetized with 4% isoflurane in a 70:30 air‐oxygen mixture in a sealed Plexiglas box.…”

Section: Methodsmentioning

confidence: 99%

“…TBI and sham-injury procedures operated in accordance with previously described methods. 7,35 In short, mice were anaesthetized with 4% isoflurane in a 70:30 air-oxygen mixture in a sealed Plexiglas box. The anaesthetized animals were positioned on the impact device, and the midpoint of the posterior fontanel and the anterior fontanel was placed directly below the hollow 60-inch height guide tube.…”

Section: Animals and Treatmentmentioning

confidence: 99%

The overexpression of RBM3 alleviates TBI‐induced behaviour impairment and AD‐like tauopathy in mice

Liu

Cao

Shi

et al. 2020

J Cellular Molecular Medi

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Alzheimer disease (AD) is the most common form of dementia in older individuals and probably develops as a result of complex interactions among multiple factors, including age, genetics, environment, lifestyle and traumatic brain injury (TBI). 1-5 The evidence has shown that there appears to be a strong link between future risk of Alzheimer's and serious TBI, but how TBI increase future risk of AD is still unclear. 6-8 TBI caused by contact sports, work accident or military blasts may induce acute or potentially long-lasting neurological dysfunction, including chronic traumatic encephalopathy. 4-6,8,9 The clinical features of TBI vary depending on the mechanistic types and severity of head injury. These features generally consist of cognitive

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“…Indeed, hypothermia may benefit severe adult TBI cases, but more research is needed to translate these findings to neonatal cases [69]. In particular, adult mice exposed to hypothermia treatment improved cognitive functions by increasing neuronal plasticity [70]. This finding may have implications in neonatal cases of TBI, as the neonatal brain is known to innately have a higher degree of plasticity than the adult brain [71].…”

Section: Caveats and Future Directionsmentioning

confidence: 99%

Treating childhood traumatic brain injury with autologous stem cell therapy

Dewan

Schimmel

Borlongan

2018

Expert Opinion on Biological Therapy

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Introduction Neonatal traumatic brain injury (TBI) is a significant cause of developmental disorders. Autologous stem cell therapy may enhance neonatal brain plasticity towards repair of the injured neonatal brain. Areas Covered The endogenous neonatal anti-inflammatory response can be enhanced by biological treatments. Stem cell therapy stands as a robust approach for sequestering the inflammation-induced cell death in the injured brain. Here, we discuss the use of umbilical cord blood cells and bone marrow stromal cells for acute and chronic treatment of experimental neonatal TBI. Autologous stem cell transplantation may retard and possibly even halt this neuroinflammation-plagued secondary cell death. Clinical translation of this stem cell therapy will require identifying the therapeutic window post-injury and harvesting ample supply of transplantable autologous stem cells. Stem cell banking with access to cryopreserved cells may allow readily available transplantable cells in addressing the unpredictable nature of neonatal TBI. Harnessing the anti-inflammatory properties of stem cells is key in combating the progressive neurodegeneration after the initial injury. Expert Opinion Combination treatments, such as with hypothermia, may enhance the therapeutic effects of stem cells. Stem cell therapy has potential as stand-alone or adjunctive therapy for treating neuroinflammation associated with acute and progressive stages of neonatal TBI.

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Hypothermia pretreatment improves cognitive impairment via enhancing synaptic plasticity in a traumatic brain injury model

Cited by 10 publications

References 51 publications

(-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice

(-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice

The overexpression of RBM3 alleviates TBI‐induced behaviour impairment and AD‐like tauopathy in mice

Treating childhood traumatic brain injury with autologous stem cell therapy

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