Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain

Xiong, Man; Cheng, Guoqiang; Ma, Simin; Yang, Yi; Shao, Xiaomei; Zhou, Wenhao

doi:10.1016/j.neuint.2011.01.026

Cited by 39 publications

(30 citation statements)

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“…Although there has been much progress in neonatal care, management strategies that minimize the morbidity of HIE have been limited. Data from multicenter clinical trials and large experimental studies have shown protective effects of mild hypothermia in the immature rat brain [3,4,5,6,7,8], but the underlying mechanisms and the critical process are not clear. Recent investigations have demonstrated that hypothermia reduces axon degeneration in animal models of axonal damage [9,10] and rescues neuron and immature oligodendrocyte (OL) loss in white matter of preterm sheep [11].…”

Section: Introductionmentioning

confidence: 99%

Short-Term Effects of Hypothermia on Axonal Injury, Preoligodendrocyte Accumulation and Oligodendrocyte Myelination after Hypoxia-Ischemia in the Hippocampus of Immature Rat Brain

Xiong¹,

Chen²,

Ma³

et al. 2013

Dev Neurosci

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Hypothermia is known to improve neurological recovery of animals and humans exposed to hypoxic-ischemic (HI) injury. However, the underlying mechanisms of the neuroprotective effects of hypothermia are only partially understood, including decreased excitotoxicity and apoptosis, and suppressed inflammation. There are few studies about the hypothermic effects on axonal injury and oligodendrocyte (OL) lineage degeneration, which are important components of neonatal brain injuries that cause cognitive disability. We hypothesized that mild hypothermia would reduce axonal injury and increase myelination in the hippocampus after HI. We performed left carotid artery ligation followed by 8% oxygen for 2 h in 7-day-old rats. Animals were divided into a hypothermic group (rectal temperature 32-33°C for 24 h) and a normothermic group (36-37°C for 24 h) immediately after HI. Animals were sacrificed at 1, 3 and 7 days for immunohistochemistry or Western blot analysis. We detected neuron loss by microtubule-associated protein 2 labeling and axonal injury by non-phosphorylated neurofilament (SMI32) with neurofilament 200 (NF200) double staining. We examined early OL progenitors by A2B5 or NG2, preoligodendrocytes (preOLs) by O4, and mature OLs by 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) and glutathione S-transferase (GST)-pi staining. Apoptosis was studied by active caspase-3. Hypothermia was associated with a significant elevation of neurons and axons in the hippocampal CA1 region after HI. Early OL progenitors (A2B5⁺) were elevated, but preOLs (O4⁺) and active caspase-3 were dramatically reduced in the hypothermic rat brain. Further study showed that the apoptotic rate of preOLs (caspase-3⁺-O4⁺/O4⁺) was markedly attenuated by hypothermic treatment compared to normothermic animals. The immunoreactivity of CNPase and GST-pi and the protein level of the myelin basic protein significantly increased in the hippocampus of hypothermia-treated rat brain. Axonal myelination also increased in hypothermic animals, which were tested by myelin basic protein and NF200 double staining and electron microscopy. These results showed that hypothermia reduced HI damage to axons and OL myelination coincided with increased early OL progenitor proliferation and decreased preOL accumulation and apoptosis. This study suggested new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection in neonatal rat brain.

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Section: Introductionmentioning

confidence: 99%

Short-Term Effects of Hypothermia on Axonal Injury, Preoligodendrocyte Accumulation and Oligodendrocyte Myelination after Hypoxia-Ischemia in the Hippocampus of Immature Rat Brain

Xiong¹,

Chen²,

Ma³

et al. 2013

Dev Neurosci

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“…Interestingly, an in vivo study found that cooling of rat brains to 33°C under hypoxic conditions led to an inhibition of hypoxia-induced apoptosis of proliferating neural stem cells and an increase in preferential maturation of neural progenitor cells into neural cells in the striatum [108]. Moreover, an in vitro study by Saito et al found that moderate hypothermia to 32°C prevented apoptosis, preserved the naivety of neural stem cells, and led to lower expression of GFAP in neural stem cell culture, indicating less glial diferentiation [109].…”

Section: Neurogenesismentioning

confidence: 99%

Hypothermia in Stroke Therapy: Systemic versus Local Application

Huber¹,

Duan²,

Chandra³

et al. 2017

Hypoxia and Human Diseases

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Presently, there are no efective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective beneits of hypothermia, and surfacecooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and eicacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identiies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well.

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“…A few experimental studies have demonstrated the beneficial effects of hypothermia on promoting neurogenesis after ischemia (Silasi and Colbourne, 2011;Silasi et al, 2012;Xiong et al, 2011). Although scientific literature regarding the role of hypothermia in neuronal connectivity repair after ischemia is scarce, it was proved that hypothermia would enhance neurite outgrowth in vitro, and upregulate genes involved in synapse organization in rat models of traumatic brain injury (Feng et al, 2010;Schmitt et al, 2010).…”

Section: Neuroprotective Mechanism Of Hypothermiamentioning

confidence: 99%