Temperature-sensitive bone mesenchymal stem cells combined with mild hypothermia reduces neurological deficit in rats of severe traumatic brain injury

Song, Bo; Wang, Xin-Xiang; Yang, Haiyan; Kong, Lingting; Sun, Hongyan

doi:10.1080/02699052.2020.1753112

Cited by 5 publications

(6 citation statements)

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“…1S). s100Beta, an astrocytic protein previously reported in blood of patients [ 37 , 38 ] and rats [ 39 ] after a TBI. Permeability of the blood brain barrier (BBB) was measured but not detected at 2 h, a timepoint previously reported to produce most BBB permeability rats after a blast TBI [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Repetitive mild TBI causes pTau aggregation in nigra without altering preexisting fibril induced Parkinson’s-like pathology burden

Delic

Karp

Guzman

et al. 2022

acta neuropathol commun

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Population studies have shown that traumatic brain injury (TBI) is associated with an increased risk for Parkinson’s disease (PD) and among U.S. Veterans with a history of TBI this risk is 56% higher. The most common type of TBI is mild (mTBI) and often occurs repeatedly among athletes, military personnel, and victims of domestic violence. PD is classically characterized by deficits in fine motor movement control resulting from progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) midbrain region. This neurodegeneration is preceded by the predictable spread of characteristic alpha synuclein (αSyn) protein inclusions. Whether repetitive mTBI (r-mTBI) can nucleate PD pathology or accelerate prodromal PD pathology remains unknown. To answer this question, an injury device was constructed to deliver a surgery-free r-mTBI to rats and human-like PD pathology was induced by intracranial injection of recombinant αSyn preformed fibrils. At the 3-month endpoint, the r-mTBI caused encephalomalacia throughout the brain reminiscent of neuroimaging findings in patients with a history of mTBI, accompanied by astrocyte expansion and microglial activation. The pathology associated most closely with PD, which includes dopaminergic neurodegeneration in the SNpc and Lewy body-like αSyn inclusion burden in the surviving neurons, was not produced de novo by r-mTBI nor was the fibril induced preexisting pathology accelerated. r-mTBI did however cause aggregation of phosphorylated Tau (pTau) protein in nigra of rats with and without preexisting PD-like pathology. pTau aggregation was also found to colocalize with PFF induced αSyn pathology without r-mTBI. These findings suggest that r-mTBI induced pTau aggregate deposition in dopaminergic neurons may create an environment conducive to αSyn pathology nucleation and may add to preexisting proteinaceous aggregate burden.

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Section: Resultsmentioning

confidence: 99%

Repetitive mild TBI causes pTau aggregation in nigra without altering preexisting fibril induced Parkinson’s-like pathology burden

Delic

Karp

Guzman

et al. 2022

acta neuropathol commun

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“…Therapeutic hypothermia and the growth factor FGF2 were each individually beneficial in improving lesion volume and resulting neurobehavioral outcomes but had no additional benefit when combined [ 98 ]. Other studies involving therapeutic hypothermia have been mixed, with a benefit versus monomodal therapies when combined with stem cells in preclinical studies [ 99 ] but worse outcomes when combined with progesterone in a large clinical trial [ 100 ]. Voluntary physical exercise, in combination with the endogenous compound citicoline, demonstrated reductions in lesion volumes and neurobehavioral outcomes after TBI, but there was no benefit to combined therapy compared to the individual interventions [ 101 ].…”

Section: Resultsmentioning

confidence: 99%

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

Narayan

2023

JCM

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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“…MHT has long been considered to have neuroprotective effects on TBI in some small clinical trials and various experimental models (Gao et al., 2021 ; Song et al., 2020 ; C.‐F. Wang et al., 2019 ).…”

Section: Discuctionmentioning

confidence: 99%

“…MHT has long been considered to have neuroprotective effects on TBI in some small clinical trials and various experimental models (Gao et al, 2021;Song et al, 2020;C.-F. Wang et al, 2019). In 2001, a multicenter study explored the difference in prognosis between normal temperature and hypothermia TBI patients and reported that individuals who were already hypothermic at admission could achieve better outcomes (Clifton et al, 2002(Clifton et al, , 2001.…”

Section: Discuctionmentioning

confidence: 99%

“…Mild hypothermia, generally referring to a temperature between 33°C and 35°C, has been proven to be an efficient technique to alleviate neuronal injury in central system injuries, including TBI, spinal cord injury, and ischemic or hemorrhage strokes (Ahmad et al., 2014 ; Sheng et al., 2012 ; Song, Wang et al., 2020 ; Wu & Grotta, 2013 ). In recent years, the literature has reported that mild hypothermia (MHT) can reduce cerebral edema and decrease intracranial pressure in clinical practice, thereby protecting brain tissues (Andrews et al., 2015 ; Jiang et al., 2006 ).…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective effects of mild hypothermia against traumatic brain injury by the involvement of the Nrf2/ARE pathway

et al. 2022

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Background Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mild hypothermia (32–35°C) has been found to show neuroprotective effects against TBI. However, the specific mechanism is still elusive. In the current study, we explored the relationship between oxidative damage after TBI and treatment with mild hypothermia as well as the underlying molecular mechanisms. Methods We used the closed cortex injury model to perform the brain injury and a temperature monitoring and control system to regulate the body temperature of mice after injury. Adult male C57BL/6 mice were adopted in this study and divided into four experimental groups. Tissue samples were harvested 24 h after injury. Results First, our results showed that treatment with mild hypothermia significantly improved neurobehavioral dysfunction and alleviated brain edema after TBI. Moreover, treatment with mild hypothermia enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and reduced the accumulation of lipid peroxidation malondialdehyde. Importantly, the expression and activation of the nuclear factor erythroid 2‐related factor 2‐antioxidant response element (Nrf2‐ARE) pathway were upregulated by mild hypothermia after TBI. Finally, treatment with hypothermia significantly decreased the cell apoptosis induced by TBI. Conclusion Our results showed that the protective effects of mild hypothermia after TBI may be achieved by the upregulation of the Nrf2‐ARE pathway and revealed Nrf2 as a potentially important target to improve the prognosis of TBI.

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Temperature-sensitive bone mesenchymal stem cells combined with mild hypothermia reduces neurological deficit in rats of severe traumatic brain injury

Cited by 5 publications

References 50 publications

Repetitive mild TBI causes pTau aggregation in nigra without altering preexisting fibril induced Parkinson’s-like pathology burden

Repetitive mild TBI causes pTau aggregation in nigra without altering preexisting fibril induced Parkinson’s-like pathology burden

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Neuroprotective effects of mild hypothermia against traumatic brain injury by the involvement of the Nrf2/ARE pathway

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