Therapeutic hypothermia for stroke: Where to go?

Han, Ziping; Liu, Xiangrong; Luo, Yumin; Ji, Xunming

doi:10.1016/j.expneurol.2015.06.006

Cited by 58 publications

(35 citation statements)

References 181 publications

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“…Hypothermia mitigates ischemic brain injury by retarding metabolism and energy depletion, suppressing the release of excitatory amino acids, diminishing oxygen free radical production, attenuating inflammatory response, regulating gene expression, preventing BBB destruction, and balancing cell survival and death pathways (Han et al, 2015). A meta-analysis of 101 publications reporting the efficacy of hypothermia in animal models with ischemic stroke showed that induced hypothermia resulted in 44% average reduction in infarct volume and 46% average improvement in functional scores (van der Worp et al, 2007).…”

Section: Management and Treatmentmentioning

confidence: 99%

“…An in vitro OPC culture study demonstrated that mild hypothermia regulates the balance between apoptosis/differentiation and proliferation, leading to an increase in cell number (Imada et al, 2010). Several experimental studies indicate that hypothermia has beneficial effects on neurogenesis, angiogenesis, and synapse organization after stroke, all of which are associated with neural network reconstruction and functional recovery (Han et al, 2015). In humans, therapeutic hypothermia has been shown to be effective and safe in patients with global cerebral ischemia induced by cardiac arrest or neonatal hypoxic-ischemic encephalopathy (Hemmen and Lyden, 2009).…”

Section: Management and Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

White matter injury in ischemic stroke

Wang

Liu

Hong

et al. 2016

Progress in Neurobiology

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212

194

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Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

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Section: Management and Treatmentmentioning

confidence: 99%

Section: Management and Treatmentmentioning

confidence: 99%

White matter injury in ischemic stroke

Wang

Liu

Hong

et al. 2016

Progress in Neurobiology

Self Cite

212

194

View full text Add to dashboard Cite

show abstract

“…To address this issue, experimental and clinical investigations have clarified an extensive list of injury processes that are sensitive to brain temperature variations during or following injury (Atkins et al, 2007; Chatzipanteli et al, 1999; Chatzipanteli et al, 2000; Polderman, 2009; Suzuki et al, 2003; Vitarbo et al, 2004). Previous review articles have thoroughly discussed these temperature sensitive processes that include excitotoxicity, free radical generation, programmed cell death and neuroinflammation (Dietrich, 1992; Dietrich et al, 2009; Dietrich and Bramlett, 2010; Han et al, 2015; Li et al, 2015; Lotocki et al, 2011; Truettner et al, 2005; Yenari and Han, 2012; Yenari and Han, 2013). In one early study using in vivo microdialysis, Globus and colleagues for example reported that extracellular levels of glutamate and indicators of free radical formation were dramatically reduced with hypothermia compared to normothermia (Globus et al, 1995).…”

Section: Mechanisms Underlying Temperature Effectsmentioning

confidence: 99%

Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation

Dietrich

Bramlett

2016

Brain Research

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The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induce hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients.

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“…Indeed, this stem cell-drug combination therapy has been a recent topic of much interest in cell therapy for stroke [8]. Recent non-pharmacological approaches shown to augment neurogenesis and to dampen inflammation in stroke have involved remote ischemic conditioning [70–75] and localized cerebral hypothermia [76]. Rigorous preclinical studies will be needed to translate combination therapies for clinical applications in stroke.…”

Section: Cell Therapy: From Standing Alone To Synergic Regenerativmentioning

confidence: 99%

Recent Advances in Stem Cell-Based Therapeutics for Stroke

Napoli

Borlongan

2016

Transl. Stroke Res.

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Regenerative medicine for central nervous system disorders, including stroke, has challenged the non-regenerative capacity of the brain. Among the many treatment strategies tailored towards repairing the injured brain, stem cell-based therapeutics have been demonstrated as safe and effective in animal models of stroke, and are being tested in limited clinical trials. We address here key lab-to-clinic translational research that relate to efficacy, safety, and mechanism of action underlying stem cell therapy. Recognizing the multi-pronged cell death processes associated with stroke that will likely require combination therapies, we next discuss potent drugs and novel technologies directed at improving the functional outcomes of stem cell-based therapeutics. We also examine discrepant transplant regimens between preclinical studies and clinical trials, as well as missing appropriate control arm (i.e., stroke subjects undergoing rehabilitation) on which to directly compare the therapeutic benefits of cell therapy. Finally, the bioethics of cell therapy is presented in order to assess its prevailing social status. With preliminary results now being reported from on-going clinical trials of stem cell therapy for stroke, a careful assessment of the true functional benefits of this novel treatment will further direct the future of regenerative medicine for neurological disorders.

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Therapeutic hypothermia for stroke: Where to go?

Cited by 58 publications

References 181 publications

White matter injury in ischemic stroke

White matter injury in ischemic stroke

Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation

Recent Advances in Stem Cell-Based Therapeutics for Stroke

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