Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

Zhao, Li-Ru; Willing, Alison E.

doi:10.1016/j.pneurobio.2018.01.004

Cited by 99 publications

(86 citation statements)

References 379 publications

(492 reference statements)

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“…We observed an increased number of BrdU-positive cells within the peri-infarct regions in stroke mice treated with GH, which is consistent with previous studies demonstrating that GH promotes cell proliferation within the central nervous system [52,53]. Critically, these progenitor cells are known to release neurotrophic factors to provide an environment which may contribute to neural network remodelling and functional recovery [54,55].…”

Section: Discussionsupporting

confidence: 91%

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Sanchez-Bezanilla

Åberg

Crock

et al. 2020

IJMS

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Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%–60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.

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Section: Discussionsupporting

confidence: 91%

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Sanchez-Bezanilla

Åberg

Crock

et al. 2020

IJMS

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“…According to the pivotal role of oxidative stress and neuroinflammation in cellular injury during cerebral ischaemia/reperfusion, antioxidant and anti‐inflammatory agents can serve as potential targets for the management of ischaemic stroke . In recent years, the neuroprotective activity of antioxidants in animal models of ischaemic stroke has been distinctly established .…”

Section: Introductionmentioning

confidence: 99%

“…[6] According to the pivotal role of oxidative stress and neuroinflammation in cellular injury during cerebral ischaemia/ reperfusion, antioxidant and anti-inflammatory agents can serve as potential targets for the management of ischaemic stroke. [7] In recent years, the neuroprotective activity of antioxidants in animal models of ischaemic stroke has been distinctly established. [8,9] Besides, clinical trials have shown that the administration of antioxidant agents improve the clinical outcomes in patients suffering from acute cerebrovascular ischaemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

Khoshnazar

Bigdeli

Parvardeh

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Oxidative stress and inflammation have a critical role in the pathogenesis of ischaemic stroke. Alpha‐pinene is a monoterpenoid molecule with anti‐inflammatory and antioxidant properties. The nobility of the present study was to evaluate the neuroprotective effect of α‐pinene in ischaemic stroke. Methods Ischaemic stroke was induced by transient middle cerebral artery occlusion followed by 24 h reperfusion in male Wistar rats. Alpha‐pinene (25, 50 and 100 mg/kg, i.p.) was administered in the beginning of reperfusion. Then, the neurobehavioural function, infarct volume, brain oedema, antioxidant enzyme activity and the concentration of malondialdehyde (MDA), nitric oxide (NO) and interleukin‐6 (IL‐6) were evaluated by different methods in the brain. Key findings Alpha‐pinene (50 and 100 mg/kg) elicited a significant decrease in the brain oedema and infarct size as well as an improvement in the neurobehavioural function. Besides, α‐pinene (100 mg/kg) restored the function of superoxide dismutase, catalase and glutathione peroxidase and reduced the concentration of MDA, NO and IL‐6 in the hippocampus, cortex and striatum. Conclusions It was ultimately attainted that α‐pinene exerts neuroprotective effect in ischaemic stroke in rat through the restoration of antioxidant enzymes activity, attenuation of lipid peroxidation and reduction of inflammation in the ischaemic brains.

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“…While p38 has already been proven as a therapeutic target for acute stroke intervention, it is unclear whether p38 also plays a critical role in impairing functional recovery during the subacute phase of stroke which embodies brain repair initiation [6][7][8]. Time course analyses of phospho-p38 (i.e.…”

Section: Pagementioning

confidence: 99%

“…Based on pathological characteristics and their timing, a stroke is classified into three clinical phases, including the acute (i.e. first 48 hours after stroke onset), the subacute (from 48 hours to >6 weeks post stroke) and the chronic phase (starts at 3-6 months post stroke) [6]. The acute phase represents an opportunity to salvage threatened tissue and reduce the extent of injury, for example via reperfusion or neuroprotection [7,8].…”

Section: Introductionmentioning

confidence: 99%

Continuous administration of the p38α inhibitor neflamapimod during the subacute phase after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery accompanied by increase in brain BDNF protein level

Krakovsky¹,

Germann²,

Levy³

2020

Preprint

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There is unmet need for effective stroke therapies. Numerous neuroprotection attempts for acute cerebral ischemia have failed and there is growing interest in developing therapies that widen the treatment initiation window and promote functional recovery through increasing synaptic plasticity. The p38 mitogen-activated protein kinase is an already proven target for acute experimental stroke intervention and was hypothesized to also contribute to neuroinflammationmediated impairment of recovery during the subacute phase. Neflamapimod, an orally bioavailable, brain-penetrant, potent and selective small molecule p38 inhibitor was evaluated as a subacute phase stroke treatment to promote recovery in this research study. Neflamapimod administration at two clinically relevant dose levels was initiated outside of the previously characterized neuroprotection window of less than 24 hours after stroke for p38 inhibitors to rats after transient middle cerebral artery occlusion. Continuous administration of neflamapimod, starting at 48 hours after reperfusion, significantly improved behavioral outcomes assessed by the modified neurological severity score at four-and six-weeks post stroke in a dose-dependent manner. Neflamapimod also demonstrated beneficial effects on additional measures of sensory and motor function and resulted in a dose-related increase in the terminal brain-derived neurotrophic factor protein level in both the injured and uninjured brain hemisphere. Variable interleukin-1 levels were detected in the injured brain hemisphere at study termination in a subset of the animals within every test group, implying ongoing, chronic inflammation, however, no clear neflamapimod effect on interleukin-1 production was observable. The dose-related in vivo efficacy of neflamapimod offers the possibility of both expanding the window for initiation of therapy after stroke and for improving recovery after a completed stroke. Since neflamapimod is already in mid-stage clinical trials for Alzheimer's disease PAGE 3 and related dementias, the current results make it especially attractive for evaluation in a proof-ofconcept clinical trial as therapeutic to promote recovery after ischemic stroke.

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Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

Cited by 99 publications

References 379 publications

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

Continuous administration of the p38α inhibitor neflamapimod during the subacute phase after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery accompanied by increase in brain BDNF protein level

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