Whole body hypothermia broadens the therapeutic window of intranasally administered IGF-1 in a neonatal rat model of cerebral hypoxia–ischemia

Lin, Shaopei; Rhodes, Philip; Cai, Zhengwei

doi:10.1016/j.brainres.2011.02.013

Cited by 21 publications

(18 citation statements)

References 43 publications

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“…We are aware that P7 rats have become a widely used model for the study of HI brain injury [17,19,29,46,49]. However, the overall increases in the severity of cerebral lesions on the side of the common carotid artery ligation are similar between P2-P3 and P7 rats, while HI brain injury produces age-dependent and region-specific injuries [45].…”

Section: Methodsmentioning

confidence: 99%

Original article Effects of hypothermia on ex vivo microglial production of pro- and anti-inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice

Matsui¹,

Kida²,

Iha³

et al. 2014

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A b s t r a c t Introduction: Activated microglia produce neurotoxic factors, including pro-inflammatory cytokines and nitric oxide (NO), in response to neuronal destruction. Therapeutic suppression of microglial release of these factors by various approaches including hypothermia is considered to be neuroprotective after severe brain damage. We examined the effects of hypothermic culture on the production of pro-and anti-inflammatory cytokines and NO in ex vivo microglia that were derived from mice with hypoxic-ischemic (HI) brain injury, through the stimulation of toll-like receptors (TLRs) that play significant roles in the pathological processes underlying a sterile central nervous system injury.Material and methods: Two-day-old mice underwent the right common carotid artery ligation followed by 6% oxygen for 30 min, and thereafter were placed at 37°C for 24 h, after which microglia were isolated and then cultured with TLR2 and TLR4 agonists at 33°C and 37°C. Cytokine and NO levels in culture supernatants were measured. Results: Compared with 37°C, hypothermia (33°C) reduced the production of tumour necrosis factor-alpha (TNF-α: a pro-inflammatory cytokine) at 6 h and interleukin-10 (IL-10: an anti-inflammatory cytokine) and NO at 48 h. Conclusions:In TLR-activated microglia that were derived from mice with HI brain injury, hypothermia reduced the production of and NO temporally, a

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Section: Methodsmentioning

confidence: 99%

Original article Effects of hypothermia on ex vivo microglial production of pro- and anti-inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice

Matsui¹,

Kida²,

Iha³

et al. 2014

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“…IGF-1, via the PI3K/Akt/GSK3β and NF-κB pathway phosphorylation, attenuates activation of caspases and mitogenic effects. Previous research has demonstrated that the neuroprotective actions of IGF-1 infusion were global, robust, and displayed a broad effective dose range and treatment window [102]. …”

Section: Clinical Strategies Of Antioxidants In Hiementioning

confidence: 99%

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Zhao

Zhu

Fujino

et al. 2016

IJMS

165

108

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Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS) production rapidly increases and overwhelms antioxidant defenses. A large excess of ROS will directly modify or degenerate cellular macromolecules, such as membranes, proteins, lipids, and DNA, and lead to a cascading inflammatory response, and protease secretion. These derivatives are involved in a complex interplay of multiple pathways (e.g., inflammation, apoptosis, autophagy, and necrosis) which finally lead to brain injury. In this review, we highlight the molecular mechanism for oxidative stress in HIE, summarize current research on therapeutic strategies utilized in combating oxidative stress, and try to explore novel potential clinical approaches.

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“…Since IGF-1 was co-administered with LPS through intracerebral injection in our study, the local concentration of IGF-1 could be high at the injection site and consequently affect the action of IGF-1. We and other investigators have shown that IGF-1 can be delivered to the rat or mouse brain along olfactory and trigeminal pathways with intranasal administration (Thorne et al, 2004; Lin et al, 2009) and that intranasally delivered IGF-1 protects against cerebral hypoxic-ischemic injury (Liu et al, 2001a, b; Lin et al, 2009, 2011) or other neurodegenerative damages (Vig et al, 2006). Therefore, the objective of the current study was to test whether a single dose of IGF-1 delivered through intranasal infusion in the neonatal rat can provide protection against LPS-induced oligodendrocyte and white matter injury and improve neurological functions in juvenile animals.…”

mentioning

confidence: 98%

Intranasal administration of insulin-like growth factor-1 protects against lipopolysaccharide-induced injury in the developing rat brain

Cai¹,

Fan²,

Lin³

et al. 2011

Neuroscience

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Our previous studies show that insulin-like growth factor-1 (IGF-1) can either protect against or increase lipopolysaccharide (LPS)-induced damage in the developing brain, depending on the dose, when it is co-administered with LPS through intracerebral injection. To further explore effects of IGF-1 on central inflammation associated brain injury, IGF-1 was administered through intranasal infusion in the current study. Postnatal day 5 (P5) rats were exposed to LPS at a dose of 1 μg/g body weight or sterile saline through intracerebral injection. Recombinant human insulin-like growth factor-1 (rhIGF-1) at a dose of 50 μg/pup or vehicle was administered intranasally 1 or 2 hr after the LPS injection. Neonatal LPS exposure resulted in oligodendrocyte (OL) and white matter injury in the P6 or P21 rat brain. The damages include dilatation of lateral ventricles, pyknotic cell death, loss of OL progenitor cells and mature OLs in the cingulum area, and impairment of myelination at the corpus callosum area. Neurological dysfunctions were observed in juvenile rats with neonatal LPS exposure. Intranasal IGF-1 treatment at either 1 or 2 hr after LPS exposure significantly attenuated LPS-induced brain injury and improved some behavioral deficits. Intranasal IGF-1 treatment also reduced infiltration of polymorphonuclear leukocytes and activation of microglia in the rat brain 24 hr after LPS exposure, but it did not prevent the elevation in concentrations of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) in the LPS-exposed rat brain during the first 24 hr. This is an indication that direct anti-inflammation might not be the primary mechanism for the protection of IGF-1, and other mechanisms, such as anti-apoptotic effects, are likely involved in its protective effects.

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Whole body hypothermia broadens the therapeutic window of intranasally administered IGF-1 in a neonatal rat model of cerebral hypoxia–ischemia

Cited by 21 publications

References 43 publications

Original article Effects of hypothermia on ex vivo microglial production of pro- and anti-inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice

Original article Effects of hypothermia on ex vivo microglial production of pro- and anti-inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Intranasal administration of insulin-like growth factor-1 protects against lipopolysaccharide-induced injury in the developing rat brain

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