Stem cells and motor recovery after stroke

Loubinoux, Isabelle; Demain, Boris; Davoust, Carole; Plas, Benjamin; Vaysse, Laurence

doi:10.1016/j.rehab.2014.08.008

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…Preclinical studies have revealed that strategies aimed to enhance neurogenesis, such as cell transplantation therapy, facilitated motor function recovery after stroke [44][45][46]. Recent findings indeed suggest that neurogenesis can also occur in the infarct and surrounding areas, including the PT stroke model [10].…”

Section: Discussionmentioning

confidence: 99%

Continuous theta-burst stimulation enhances and sustains neurogenesis following ischemic stroke

Zong¹,

Gu²,

Zhou³

et al. 2022

Theranostics

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Rationale: Previous work has indicated that continuous theta-burst stimulation (cTBS), a modality of transcranial magnetic stimulation (TMS), may provide neuroprotection and improve neurological function after stroke by preserving the blood-brain barrier, altering glial polarization phenotypes, and supporting peri-infarct angiogenesis. The present study was performed to examine whether cTBS, a noninvasive neurostimulation technique, promotes neurogenesis in a photothrombotic (PT) stroke rat model and contributes to functional recovery. Methods: Beginning 3 h or 1 week after the induction of PT stroke, once-daily 5-min cTBS treatments were applied to the infarcted hemisphere for 6 days. Samples were collected 6 days, 22 days, and 35 days after PT stroke. Fluorescent labeling, Western blotting, and behavioral tests were performed accordingly. Results: We found that cTBS therapy significantly expanded the pool of neural progenitor cells (NPCs) and newly generated immature neurons in the cortical peri-infarct region after PT stroke. Likewise, the amount of DCX-positive immature neurons in the peri-infarct area was markedly elevated by cTBS. Application of cTBS strikingly diminished the PT-induced loss of NPCs and newly-formed neurons. In addition, the amount of newly generated mature neurons in the peri-infarct zone was significantly promoted by cTBS. Intriguingly, cTBS reduced reactive gliogenesis significantly while promoting oligodendrogenesis and preserving myelination. Mechanistic studies uncovered that cTBS upregulated brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2). Finally, cTBS-treated animals displayed improved motor functions. To be noted, temozolomide (TMZ), a drug that has been previously used to suppress neurogenesis, could reverse the beneficial effects of cTBS. Conclusions: Our findings provide new insight into the mechanism by which cTBS promotes functional recovery from stroke. We demonstrated that cTBS effectively enhances and sustains neurogenesis after PT stroke. Both early and delayed cTBS treatment could improve the survival of newly generated neurons and functional recovery, and inhibition of neurogenesis could reverse these therapeutic benefits. Mechanistically, cTBS was effective in upregulating the release of neurotrophic factors, protecting NPC and immature neurons, as well as suppressing excessive gliogenesis.

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Section: Discussionmentioning

confidence: 99%

Continuous theta-burst stimulation enhances and sustains neurogenesis following ischemic stroke

Zong¹,

Gu²,

Zhou³

et al. 2022

Theranostics

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“…On the other hand, numerous scientific reports corroborated the therapeutic benefit provided by stem cell populations in stroke. This is exemplified by the improvement of neurofunctional deficits ( 4 ), reduction of infarct volume, an extension of the time windows for intervention ( 5 , 6 ), pro-regenerative cerebral reorganization ( 7 ), and potentially even limited tissue restoration ( 8 ), as well as mitigation of post-stroke neuroinflammation ( 9 ). Consequently, first early stage clinical studies are underway to confirm safety and to collect evidence for the therapeutic benefit of stem cell-based treatments in human stroke patients ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

The dark side of the force – constraints and complications of cell therapies for stroke

Boltze

2015

Front. Neurol.

132

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Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients.

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“…In addition, antidepressant drugs targeting DA and its receptors also showed great benefits in PSD treatment. For example, fluoxetine and paroxetine, two of the most commonly used drugs in PSD treatment, could prevent the degeneration of nigrostriatal dopaminergic neurons ( 140 ). A recent study has revealed that SNRIs achieve a fast antidepressant effect by elevating the DA concentrations in the mPFC and the Nac ( 96 ).…”

Section: Monoamine Transmitters In the Treatment Of Psdmentioning

confidence: 99%

The Relationship Between 5-Hydroxytryptamine and Its Metabolite Changes With Post-stroke Depression

Zheng-ming

et al. 2022

Front. Psychiatry

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Post-stroke depression (PSD) is the most common and serious sequelae of stroke. Approximately 33% of stroke survivors were affected by PSD. However, many issues (e.g., incidence, diagnostic marker, and risk factor) related to PSD remained unclear. The “monoamine hypothesis” is a significant hypothesis for depression, which suggests that three monoamines play a key role in depression. Therefore, most current antidepressants are developed to modulate the monoamines on PSD treatment, and these antidepressants have good effects on patients with PSD. However, the potential mechanisms of three monoamines in PSD are still unclear. Previously, we proposed “three primary emotions,” which suggested a new model of basic emotions based on the three monoamines. It may provide a new way for PSD treatment. In addition, recent studies have found that monoamine-related emotional intervention also showed potential effects in the treatment and prevention of PSD. This study discusses these issues and attempts to provide a prospect for future research on PSD.

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Stem cells and motor recovery after stroke

Cited by 8 publications

References 40 publications

Continuous theta-burst stimulation enhances and sustains neurogenesis following ischemic stroke

Continuous theta-burst stimulation enhances and sustains neurogenesis following ischemic stroke

The dark side of the force – constraints and complications of cell therapies for stroke

The Relationship Between 5-Hydroxytryptamine and Its Metabolite Changes With Post-stroke Depression

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